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PSMD1 and PSMD2 regulate HepG2 cell proliferation and apoptosis via modulating cellular lipid droplet metabolism

Obesity and nonalcoholic steatohepatitis (NASH) are well-known risk factors of hepatocellular carcinoma (HCC). The lipid-rich environment enhances the proliferation and metastasis abilities of tumor cells. Pre...

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The effect of BACE1-AS on β-amyloid generation by regulating BACE1 mRNA expression

The BACE1 antisense transcript (BACE1-AS) is a conserved long noncoding RNA (lncRNA). The level of BACE1-AS is significantly increased and the level of the BACE1 mRNA is slightly increased in subjects with AD....

Overlapping transcriptional expression response of wheat zinc-induced facilitator-like transporters emphasize important role during Fe and Zn stress

Hexaploid wheat is an important cereal crop that has been targeted to enhance grain micronutrient content including zinc (Zn) and iron (Fe). In this direction, modulating the expression of plant transporters i...

MiR-32-5p influences high glucose-induced cardiac fibroblast proliferation and phenotypic alteration by inhibiting DUSP1

The current study aimed to investigate the effects of miR-32-5p on cardiac fibroblasts (CFs) that were induced with high levels of glucose; we also aimed to identify the potential mechanisms involved in the re...

Correction to: A protocol for custom CRISPR Cas9 donor vector construction to truncate genes in mammalian cells using pcDNA3 backbone

The original article [1] contains three erroneous mentions of usage of a restriction enzyme— Bst Z17I—in the Methods section as displayed in the following sentences.

The original article was published in BMC Molecular Biology 2018 19 :3

Comparison of miRNA - 101a - 3p and miRNA - 144a - 3p regulation with the key genes of alpaca melanocyte pigmentation

Many miRNA functions have been revealed to date. Single miRNAs can participate in life processes by regulating more than one target gene, and more than one miRNA can also simultaneously act on one target mRNA....

Correction to: MicroRNA-325-3p protects the heart after myocardial infarction by inhibiting RIPK3 and programmed necrosis in mice

The original article [1] contains an error whereby Fig. 7 displays incorrect results; the correct version of Fig. 7 can be viewed ahead in this Correction article and should be considered in place of the origi...

The original article was published in BMC Molecular Biology 2019 20 :17

MicroRNA-325-3p protects the heart after myocardial infarction by inhibiting RIPK3 and programmed necrosis in mice

Receptor-interacting serine-threonine kinase 3 (RIPK3)-mediated necroptosis has been implicated in the progression of myocardial infarction (MI), but the underlying mechanisms, particularly whether microRNAs (...

The Correction to this article has been published in BMC Molecular Biology 2019 20 :18

Giant group I intron in a mitochondrial genome is removed by RNA back-splicing

The mitochondrial genomes of mushroom corals (Corallimorpharia) are remarkable for harboring two complex group I introns; ND5-717 and COI-884. How these autocatalytic RNA elements interfere with mitochondrial ...

Exploration of carbohydrate binding behavior and anti-proliferative activities of Arisaema tortuosum lectin

Lectins have come a long way from being identified as proteins that agglutinate cells to promising therapeutic agents in modern medicine. Through their specific binding property, they have proven to be anti-ca...

Characterization of cadmium-responsive MicroRNAs and their target genes in maize ( Zea mays ) roots

Current research has shown that microRNAs (miRNAs) play vital roles in plant response to stress caused by heavy metals such as aluminum, arsenic, cadmium (Cd), and mercury. Cd has become one of the most hazard...

Identification and validation of reference genes for real-time quantitative RT-PCR analysis in jute

With the availability of genome sequences, gene expression analysis of jute has drawn considerable attention for understanding the regulatory mechanisms of fiber development and improving fiber quality. Gene e...

Small nucleolar RNA Sf-15 regulates proliferation and apoptosis of Spodoptera frugiperda Sf9 cells

Small nucleolar RNAs (snoRNAs) function in guiding 2′- O -methylation and pseudouridylation of ribosomal RNAs (rRNAs) and small nuclear RNAs (snRNAs). In recent years, more and more snoRNAs have been found to play ...

Key genes differential expressions and pathway involved in salt and water-deprivation stresses for renal cortex in camel

Camels possess the characteristics of salt- and drought-resistances, due to the long-time adaption to the living environment in desert. The camel resistance research on transcriptome is rare and deficient, esp...

Development of a novel selection/counter-selection system for chromosomal gene integrations and deletions in lactic acid bacteria

The underlying mechanisms by which probiotic lactic acid bacteria (LAB) enhance the health of the consumer have not been fully elucidated. Verification of probiotic modes of action can be achieved by using sin...

Selection of reference genes for the quantitative real-time PCR normalization of gene expression in Isatis indigotica fortune

Isatis indigotica , a traditional Chinese medicine, produces a variety of active ingredients. However, little is known about the key genes and corresponding expression profiling involved in the biosynthesis pathwa...

MEF2A alters the proliferation, inflammation-related gene expression profiles and its silencing induces cellular senescence in human coronary endothelial cells

Myocyte enhancer factor 2A (MEF2A) plays an important role in cell proliferation, differentiation and survival. Functional deletion or mutation in MEF2A predisposes individuals to cardiovascular disease mainly...

Transcriptomic responses to grazing reveal the metabolic pathway leading to the biosynthesis of domoic acid and highlight different defense strategies in diatoms

A major cause of phytoplankton mortality is predation by zooplankton. Strategies to avoid grazers have probably played a major role in the evolution of phytoplankton and impacted bloom dynamics and trophic ene...

RNA sequencing, selection of reference genes and demonstration of feeding RNAi in Thrips tabaci (Lind.) (Thysanoptera: Thripidae)

Thrips tabaci is a severe pest of onion and cotton. Due to lack of information on its genome or transcriptome, not much is known about this insect at the molecular level. To initiate molecular studies in this ins...

A fragment activity assay reveals the key residues of TBC1D15 GTPase-activating protein (GAP) in Chiloscyllium plagiosum

GTPase-activating proteins (GAPs) with a TBC (Tre-2/Bub2/Cdc16) domain architecture serve as negative regulators of Rab GTPases. The related crystal structure has been studied and reported by other members of ...

HexA is required for growth, aflatoxin biosynthesis and virulence in Aspergillus flavus

Woronin bodies are fungal-specific organelles whose formation is derived from peroxisomes. The former are believed to be involved in the regulation of mycotoxins biosynthesis, but not in their damage repair fu...

Genome-wide identification of brain miRNAs in response to high-intensity intermittent swimming training in Rattus norvegicus by deep sequencing

Physical exercise can improve brain function by altering brain gene expression. The expression mechanisms underlying the brain’s response to exercise still remain unknown. miRNAs as vital regulators of gene ex...

Graphene oxide down-regulates genes of the oxidative phosphorylation complexes in a glioblastoma

Recently different forms of nanographene were proposed as the material with high anticancer potential. However, the mechanism of the suppressive activity of the graphene on cancer development remains unclear. ...

MiRNAs differentially expressed in skeletal muscle of animals with divergent estimated breeding values for beef tenderness

MicroRNAs (miRNAs) are small noncoding RNAs of approximately 22 nucleotides, highly conserved among species, which modulate gene expression by cleaving messenger RNA target or inhibiting translation. MiRNAs ar...

The Dictyostelium discoideum homologue of Twinkle, Twm1, is a mitochondrial DNA helicase, an active primase and promotes mitochondrial DNA replication

DNA replication requires contributions from various proteins, such as DNA helicases; in mitochondria Twinkle is important for maintaining and replicating mitochondrial DNA. Twinkle helicases are predicted to a...

Matrix association region/scaffold attachment region (MAR/SAR) sequence: its vital role in mediating chromosome breakages in nasopharyngeal epithelial cells via oxidative stress-induced apoptosis

Oxidative stress is known to be involved in most of the aetiological factors of nasopharyngeal carcinoma (NPC). Cells that are under oxidative stress may undergo apoptosis. We have previously demonstrated that...

Molecular analysis of NPAS3 functional domains and variants

NPAS3 encodes a transcription factor which has been associated with multiple human psychiatric and neurodevelopmental disorders. In mice, deletion of Npas3 was found to cause alterations in neurodevelopment, as w...

Integration of transcriptome and proteome profiles in glioblastoma: looking for the missing link

Glioblastoma (GB) is the most common and aggressive tumor of the brain. Genotype-based approaches and independent analyses of the transcriptome or the proteome have led to progress in understanding the underly...

Analyses of changes in myocardial long non-coding RNA and mRNA profiles after severe hemorrhagic shock and resuscitation via RNA sequencing in a rat model

Ischemia–reperfusion injury has been proven to induce organ dysfunction and death, although the mechanism is not fully understood. Long non-coding RNAs (lncRNAs) have drawn wide attention with their important ...

Coincidence cloning recovery of Brucella melitensis RNA from goat tissues: advancing the in vivo analysis of pathogen gene expression in brucellosis

Brucella melitensis bacteria cause persistent, intracellular infections in small ruminants as well as in humans, leading to significant morbidity and economic loss worldwide. The majority of experiments on the tr...

Positive cofactor 4 (PC4) contributes to the regulation of replication-dependent canonical histone gene expression

Core canonical histones are required in the S phase of the cell cycle to pack newly synthetized DNA, therefore the expression of their genes is highly activated during DNA replication. In mammalian cells, this...

Evaluation of suitable reference genes for qRT-PCR normalization in strawberry ( Fragaria  ×  ananassa ) under different experimental conditions

Strawberry has received much attention due to its nutritional value, unique flavor, and attractive appearance. The availability of the whole genome sequence and multiple transcriptome databases allows the grea...

Laser capture microdissection for transcriptomic profiles in human skin biopsies

The acquisition of reliable tissue-specific RNA sequencing data from human skin biopsy represents a major advance in research. However, the complexity of the process of isolation of specific layers from fresh-...

Targeting miR-9 in gastric cancer cells using locked nucleic acid oligonucleotides

Gastric cancer is the third leading cause of cancer-related mortality worldwide. Recently, it has been demonstrated that gastric cancer cells display a specific miRNA expression profile, with increasing eviden...

Quantitative profiling of BATF family proteins/JUNB/IRF hetero-trimers using Spec-seq

BATF family transcription factors (BATF, BATF2 and BATF3) form hetero-trimers with JUNB and either IRF4 or IRF8 to regulate cell fate in T cells and dendritic cells in vivo. While each combination of the heter...

pH-mediated upregulation of AQP1 gene expression through the Spi-B transcription factor

Bicarbonate-based peritoneal dialysis (PD) fluids enhance the migratory capacity and damage-repair ability of human peritoneal mesothelial cells by upregulating AQP1. However, little is known about the underly...

A protocol for custom CRISPR Cas9 donor vector construction to truncate genes in mammalian cells using pcDNA3 backbone

Clustered regularly interspaced short palindromic repeat (CRISPR) RNA-guided adaptive immune systems are found in prokaryotes to defend cells from foreign DNA. CRISPR Cas9 systems have been modified and employ...

The Correction to this article has been published in BMC Molecular Biology 2019 20 :20

Recommendations for mRNA analysis of micro-dissected glomerular tufts from paraffin-embedded human kidney biopsy samples

Glomeruli are excellent pre-determined natural structures for laser micro-dissection. Compartment-specific glomerular gene expression analysis of formalin-fixed paraffin-embedded renal biopsies could improve r...

Nutrient depletion and TOR inhibition induce 18S and 25S ribosomal RNAs resistant to a 5′-phosphate-dependent exonuclease in Candida albicans and other yeasts

Messenger RNA (mRNA) represents a small percentage of RNAs in a cell, with ribosomal RNA (rRNA) making up the bulk of it. To isolate mRNA from eukaryotes, typically poly-A selection is carried out. Recently, a...

An optimized rapid bisulfite conversion method with high recovery of cell-free DNA

Methylation analysis of cell-free DNA is a encouraging tool for tumor diagnosis, monitoring and prognosis. Sensitivity of methylation analysis is a very important matter due to the tiny amounts of cell-free DN...

Sumoylation in p27kip1 via RanBP2 promotes cancer cell growth in cholangiocarcinoma cell line QBC939

Cholangiocarcinoma is one of the deadly disease with poor 5-year survival and poor response to conventional therapies. Previously, we found that p27kip1 nuclear-cytoplasmic translocation confers proliferation ...

An optimised protocol for isolation of RNA from small sections of laser-capture microdissected FFPE tissue amenable for next-generation sequencing

Formalin-fixed paraffin embedded (FFPE) tissue constitutes a vast treasury of samples for biomedical research. Thus far however, extraction of RNA from FFPE tissue has proved challenging due to chemical RNA–pr...

Physical shearing imparts biological activity to DNA and ability to transmit itself horizontally across species and kingdom boundaries

We have recently reported that cell-free DNA (cfDNA) fragments derived from dying cells that circulate in blood are biologically active molecules and can readily enter into healthy cells to activate DNA damage...

Interaction between NFATc2 and the transcription factor Sp1 in pancreatic carcinoma cells PaTu 8988t

Nuclear factors of activated T-cells (NFATs) have been mainly characterized in the context of immune response regulation because, as transcription factors, they have the ability to induce gene transcription. N...

Splicing arrays reveal novel RBM10 targets, including SMN2 pre-mRNA

RBM10 is an RNA binding protein involved in message stabilization and alternative splicing regulation. The objective of the research described herein was to identify novel targets of RBM10-regulated splicing. ...

Growth arrest specific gene 2 in tilapia ( Oreochromis niloticus ): molecular characterization and functional analysis under low-temperature stress

Growth arrest specific 2 ( gas2 ) gene is a component of the microfilament system that plays a major role in the cell cycle, regulation of microfilaments, and cell morphology during apoptotic processes. However, li...

Identification of G-quadruplex structures that possess transcriptional regulating functions in the Dele and Cdc6 CpG islands

G-quadruplex is a DNA secondary structure that has been shown to play an important role in biological systems. In a previous study, we identified 1998 G-quadruplex-forming sequences using a mouse CpG islands D...

Mitochondrial RNA processing in absence of tRNA punctuations in octocorals

Mitogenome diversity is staggering among early branching animals with respect to size, gene density, content and order, and number of tRNA genes, especially in cnidarians. This last point is of special interes...

Microarray expression profiling in the denervated hippocampus identifies long noncoding RNAs functionally involved in neurogenesis

The denervated hippocampus provides a proper microenvironment for the survival and neuronal differentiation of neural progenitors. While thousands of lncRNAs were identified, only a few lncRNAs that regulate n...

Early growth response protein 1 regulates promoter activity of α -plasma membrane calcium ATPase 2, a major calcium pump in the brain and auditory system

Along with sodium/calcium (Ca 2+ ) exchangers, plasma membrane Ca 2+ ATPases (ATP2Bs) are main regulators of intracellular Ca 2+ levels. There are four ATP2B paralogs encoded by four different genes. Atp2b2 encodes t...

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Page 1 of 24

Mice lacking DIO3 exhibit sex-specific alterations in circadian patterns of corticosterone and gene expression in metabolic tissues

Disruption of circadian rhythms is associated with neurological, endocrine and metabolic pathologies. We have recently shown that mice lacking functional type 3 deiodinase (DIO3), the enzyme that clears thyroi...

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Optimization of seeding density of OP9 cells to improve hematopoietic differentiation efficiency

OP9 mouse stromal cell line has been widely used to induce differentiation of human embryonic stem cells (hESCs) into hematopoietic stem/progenitor cells (HSPCs). However, the whole co-culture procedure usuall...

Development of an in vitro human alveolar epithelial air-liquid interface model using a small molecule inhibitor cocktail

The alveolar epithelium is exposed to numerous stimuli, such as chemicals, viruses, and bacteria that cause a variety of pulmonary diseases through inhalation. Alveolar epithelial cells (AECs) cultured in vitr...

Mechanical stretch leads to increased caveolin-1 content and mineralization potential in extracellular vesicles from vascular smooth muscle cells

Hypertension-induced mechanical stress on vascular smooth muscle cells (VSMCs) is a known risk factor for vascular remodeling, including vascular calcification. Caveolin-1 (Cav-1), an integral structural compo...

Melatonin reduces lung injury in type 1 diabetic mice by the modulation of autophagy

In recent years, the role of autophagy has been highlighted in the pathogenesis of diabetes and inflammatory lung diseases. In this study, using a diabetic model of mice, we investigated the expression of auto...

TonEBP/NFAT5 expression is associated with cisplatin resistance and migration in macrophage-induced A549 cells

Macrophages promote angiogenesis, metastasis, and drug resistance in several cancers. Similarly, TonEBP/NFAT5 induces metastasis in renal carcinoma and colon cancer cells. However, the role of this transcripti...

Optimizing combination therapy in prostate cancer: mechanistic insights into the synergistic effects of Paclitaxel and Sulforaphane-induced apoptosis

Combination therapies in cancer treatment have demonstrated synergistic or additive outcomes while also reducing the development of drug resistance compared to monotherapy. This study explores the potential of...

CTC together with Shh and Nrf2 are prospective diagnostic markers for HNSCC

The lack of appropriate prognostic biomarkers remains a significant obstacle in the early detection of Head and Neck Squamous Cell Carcinoma (HNSCC), a cancer type with a high mortality rate. Despite considera...

Prioritization of Trypanosoma brucei editosome protein interactions interfaces at residue resolution through proteome-scale network analysis

Trypanosoma brucei is the causative agent for trypanosomiasis in humans and livestock, which presents a growing challenge due to drug resistance. While identifying novel drug targets is vital, the process is dela...

Sumoylation of SAP130 regulates its interaction with FAF1 as well as its protein stability and transcriptional repressor function

Fas-associated factor 1 (FAF1) is a multidomain protein that interacts with diverse partners to affect numerous cellular processes. Previously, we discovered two Small Ubiquitin-like Modifier (SUMO)-interactin...

Loss of Dec1 inhibits alcohol-induced hepatic lipid accumulation and circadian rhythm disorder

Chronic alcohol exposure increases liver damage such as lipid accumulation and hepatitis, resulting in hepatic cirrhosis. Chronic alcohol intake is known to disturb circadian rhythms in humans and animals. DEC...

Association between plasma L-carnitine levels and mitochondrial DNA copy number

Mitochondria are key cytoplasmic organelles in eukaryotic cells that generate adenosine triphosphate (ATP) through the electron transport chain and oxidative phosphorylation. Mitochondrial DNA (mtDNA) copy num...

Effect of Emi1 gene silencing on the proliferation and invasion of human breast cancer cells

Breast cancer is the most common malignant tumour in women. The early silk-splitting inhibitor protein 1 Emi1 is responsible for mediating ubiquitin protein degradation. The present study investigated the effe...

TNFα induces Caspase-3 activity in hematopoietic progenitor cells CD34+, CD33+, and CD41 + of myelodysplastic syndromes

Cytopenia is the primary feature of Myelodysplastic Syndrome, even in the presence of hypercellular bone marrow. TNFα is recognized as both a proinflammatory, and proapoptotic cytokine with a well established ...

From network analysis to experimental validation: identification of regulators of non-muscle myosin II contractility using the folded-gastrulation signaling pathway

The morphogenetic process of apical constriction, which relies on non-muscle myosin II (NMII) generated constriction of apical domains of epithelial cells, is key to the development of complex cellular pattern...

Simple, low-cost, and well-performing method, the outgrowth technique, for the isolation of cells from nasal polyps

Epithelial cells are an important part of the pathomechanism in chronic rhinosinusitis with nasal polyps. It is therefore essential to establish a robust method for the isolation and culture of epithelial cell...

Comprehensive brain tissue metabolomics and biological network technology to decipher the mechanism of hydrogen-rich water on Radiation-induced cognitive impairment in rats

Hydrogen-rich water (HRW) has been shown to prevent cognitive impairment caused by ionizing radiation. This study aimed to investigate the pharmacological effects and mechanisms of HRW on ionizing radiation by...

Mineral elements and adiposity-related consequences in adolescents with intellectual disabilities

Patients with intellectual disabilities are shown to have a limited capacity for cooperation, communication,and other biological consequences, which significantly require a specialized interest in healthcare p...

Glycyrrhizin inhibits LPS-induced inflammatory responses in goat ruminal epithelial cells in vitro

Inflammation plays a crucial role in the progression of Subacute Ruminal Acidosis (SARA). The experiment was designed to investigate anti-inflammatory effects of glycyrrhizin on goats ruminal epithelial cells ...

D-galactose-induced mitochondrial oxidative damage and apoptosis in the cochlear stria vascularis of mice

Age-related hearing loss, known as presbycusis, is the result of auditory system degeneration. Numerous studies have suggested that reactive oxygen species (ROS) and mitochondrial oxidative damage play importa...

Keratin 19 binds and regulates cytoplasmic HNRNPK mRNA targets in triple-negative breast cancer

Heterogeneous nuclear ribonucleoprotein K (HNRNPK) regulates pre-mRNA processing and long non-coding RNA localization in the nucleus. It was previously shown that shuttling of HNRNPK to the cytoplasm promotes ...

A computational peptide model induces cancer cells’ apoptosis by docking Kringle 5 to GRP78

Cells can die through a process called apoptosis in both pathological and healthy conditions. Cancer development and progression may result from abnormal apoptosis. The 78-kDa glucose-regulated protein (GRP78)...

BMP9 maintains the phenotype of HTR-8/Svneo trophoblast cells by activating the SDF1/CXCR4 pathway

Bone morphogenetic protein 9 (BMP9) has been shown to regulate processes such as angiogenesis, endothelial dysfunction, and tumorigenesis. However, the role of BMP9 in preeclampsia (PE) is unclear. The purpose...

Emodin and aloe-emodin, two potential molecules in regulating cell migration of skin cells through the MAP kinase pathway and affecting Caenorhabditis elegans thermotolerance

Emodin and aloe-emodin are two anthraquinones having positive effects in wound healing. However, their mechanism of action of wound healing is not fully understood. The MAP kinase family, which plays an active...

Knockdown of ELF4 aggravates renal injury in ischemia/reperfusion mice through promotion of pyroptosis, inflammation, oxidative stress, and endoplasmic reticulum stress

Renal ischemia/reperfusion (I/R) injury is a major cause of acute kidney injury (AKI). Dysfunction of E74-like ETS transcription factor 4 (ELF4) leads to inflammation. This research intended to look into the f...

Janus Kinase 3 phosphorylation and the JAK/STAT pathway are positively modulated by follicle-stimulating hormone (FSH) in bovine granulosa cells

Janus kinase 3 (JAK3) is a member of the JAK family of tyrosine kinase proteins involved in cytokine receptor-mediated intracellular signal transduction through the JAK/STAT signaling pathway. JAK3 was previou...

Genetic and protein interaction studies between the ciliary dyslexia candidate genes DYX1C1 and DCDC2

DYX1C1 (DNAAF4) and DCDC2 are two of the most replicated dyslexia candidate genes in genetic studies. They both have demonstrated roles in neuronal migration, in cilia growth and function and they both are cytosk...

SUMOylation of PDGF receptor α affects signaling via PLCγ and STAT3, and cell proliferation

The platelet-derived growth factor (PDGF) family of ligands exerts their cellular effects by binding to α- and β-tyrosine kinase receptors (PDGFRα and PDGFRβ, respectively). SUMOylation is an important posttra...

Myogenic differentiation of human myoblasts and Mesenchymal stromal cells under GDF11 on Poly-ɛ-caprolactone-collagen I-Polyethylene-nanofibers

For the purpose of skeletal muscle engineering, primary myoblasts (Mb) and adipogenic mesenchymal stem cells (ADSC) can be co-cultured and myogenically differentiated. Electrospun composite nanofiber scaffolds...

Computational analysis of missense variant CYP4F2*3 (V433M) in association with human CYP4F2 dysfunction: a functional and structural impact

Cytochrome P450 4F2 (CYP4F2) enzyme is a member of the CYP4 family responsible for the metabolism of fatty acids, therapeutic drugs, and signaling molecules such as arachidonic acid, tocopherols, and vitamin K...

Using RNA-seq to identify suitable housekeeping genes for hypoxia studies in human adipose-derived stem cells

Hypoxic culture conditions have been used to study the impact of oxygen deprivation has on gene expression in a number of disease models. However, hypoxia response elements present in the promoter regions of s...

SCAT8/miR-125b-5p axis triggers malignant progression of nasopharyngeal carcinoma through SCARB1

Nasopharyngeal carcinoma is a tumor with high malignancy and poor prognosis, which severely affects the health of the patients. LncRNAs and microRNAs are crucial for the occurrence and development of nasophary...

ARNTL2 upregulation of ACOT7 promotes NSCLC cell proliferation through inhibition of apoptosis and ferroptosis

Recent studies have reported that the circadian transcription factor aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2) promotes the metastatic progression of lung adenocarcinoma. However, the mole...

Evolutionary relevance of single nucleotide variants within the forebrain exclusive human accelerated enhancer regions

Human accelerated regions (HARs) are short conserved genomic sequences that have acquired significantly more nucleotide substitutions than expected in the human lineage after divergence from chimpanzees. The f...

The DNA demethylation-regulated SFRP2 dictates the progression of endometriosis via activation of the Wnt/β-catenin signaling pathway

Endometriosis cause decreases in life quality and pelvic pain in reproductive-age women. Methylation abnormalities played a functional role in the progression of endometriosis, this study aimed to explore the ...

Pre-treatment with IL-6 potentiates β-cell death induced by pro-inflammatory cytokines

Type I Diabetes mellitus (T1D) is characterized by a specific destruction of β-cells by the immune system. During this process pro-inflammatory cytokines are released in the pancreatic islets and contribute for β...

Role of the human solute carrier family 14 member 1 gene in hypoxia-induced renal cell carcinoma occurrence and its enlightenment to cancer nursing

Hypoxia is considered a critical contributor to renal cell carcinoma progression, including invasion and metastasis. However, the potential mechanisms by which it promotes invasion and metastasis have not yet ...

Cyclic tensile force modifies calvarial osteoblast function via the interplay between ERK1/2 and STAT3

Mechanical therapies, such as distraction osteogenesis, are widely used in dental clinics. During this process, the mechanisms by which tensile force triggers bone formation remain of interest. Herein, we inve...

Urine-derived mesenchymal stem cells-derived exosomes enhances survival and proliferation of aging retinal ganglion cells

This study was designed to investigate to test the effect of exosomes from urine-derived mesenchymal stem cells (USCs) on the survival and viability of aging retinal ganglion cells (RGCs), and explored the pre...

RPL11 promotes non-small cell lung cancer cell proliferation by regulating endoplasmic reticulum stress and cell autophagy

Abnormal biogenesis and ribosome free function of ribosomal proteins (RPs) is important for tumorgenesis and development. Ribosomal protein L11 (RPL11) is a component of ribosomal 60 S large subunit with diffe...

Sperm capacitation and transcripts levels are altered by in vitro THC exposure

Delta-9-tetrahydrocannabinol (THC) is the primary phytocannabinoid responsible for the psychoactive properties of cannabis and is known to interact with the endocannabinoid system, which is functionally presen...

The dual role of Nrf2 in melanoma: a systematic review

Melanoma is the most lethal type of skin cancer that originates from the malignant transformation of melanocytes. Although novel treatments have improved patient survival in melanoma, the overall prognosis rem...

Hyperoxia exposure upregulates Dvl-1 and activates Wnt/β-catenin signaling pathway in newborn rat lung

Bronchopulmonary dysplasia is a serious and lifelong pulmonary disease in premature neonates that influences around one-quarter of premature newborns. The wingless-related integration site /β-catenin signaling...

Circ-ATL1 silencing reverses the activation effects of SIRT5 on smooth muscle cellular proliferation, migration and contractility in intracranial aneurysm by adsorbing miR-455

Alterations in vascular smooth muscle cells (VSMCs) contribute to the pathogenesis of intracranial aneurysms (IAs). However, molecular mechanisms underlying these changes remain unknown. The present study aime...

HMGB1 mediates lipopolysaccharide-induced macrophage autophagy and pyroptosis

Autophagy and pyroptosis of macrophages play important protective or detrimental roles in sepsis. However, the underlying mechanisms remain unclear. High mobility group box protein 1 (HMGB1) is associated with...

N-Acetyl-L-cysteine facilitates tendon repair and promotes the tenogenic differentiation of tendon stem/progenitor cells by enhancing the integrin α5/β1/PI3K/AKT signaling

Tendon injury is associated with oxidative stress, leading to reactive oxygen species (ROS) production and inflammation. N-acetyl-L-cysteine (NAC) is a potent antioxidant. However, how NAC affects the biologic...

The 3- O sulfation of heparan sulfate proteoglycans contributes to the cellular internalization of tau aggregates

Considering the high correlation between the functional decline in Alzheimer’s disease (AD) and the propagation of aggregated tau protein, many research efforts are focused on determining the underlying molecu...

microRNA-338-3p suppresses lipopolysaccharide-induced inflammatory response in HK-2 cells

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Molecular Biosciences Theses and Dissertations

Theses/dissertations from 2023 2023.

Exploring strain variation and bacteriophage predation in the gut microbiome of Ciona robusta , Celine Grace F. Atkinson

Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation and Progression , Janine M. DeBlasi

Thermodynamic frustration of TAD2 and PRR contribute to autoinhibition of p53 , Emily Gregory

Utilization of Detonation Nanodiamonds: Nanocarrier for Gene Therapy in Non-Small Cell Lung Cancer , Allan E. Gutierrez

Role of HLA-DRB1 Fucosylation in Anti-Melanoma Immunity , Daniel K. Lester

Targeting BET Proteins Downregulates miR-33a To Promote Synergy with PIM Inhibitors in CMML , Christopher T. Letson

Regulated Intramembrane Proteolysis by M82 Peptidases: The Role of PrsS in the Staphylococcus aureus Stress Response , Baylie M. Schott

Histone Deacetylase 8 is a Novel Therapeutic Target for Mantle Cell Lymphoma and Preserves Natural Killer Cell Cytotoxic Function , January M. Watters

Theses/Dissertations from 2022 2022

Regulation of the Heat Shock Response via Lysine Acetyltransferase CBP-1 and in Neurodegenerative Disease in Caenorhabditis elegans , Lindsey N. Barrett

Determining the Role of Dendritic Cells During Response to Treatment with Paclitaxel/Anti-TIM-3 , Alycia Gardner

Cell-free DNA Methylation Signatures in Cancer Detection and Classification , Jinyong Huang

The Role Of Eicosanoid Metabolism in Mammalian Wound Healing and Inflammation , Kenneth D. Maus

A Holistic Investigation of Acidosis in Breast Cancer , Bryce Ordway

Characterizing the Impact of Postharvest Temperature Stress on Polyphenol Profiles of Red and White-Fruited Strawberry Cultivars , Alyssa N. Smith

Theses/Dissertations from 2021 2021

Multifaceted Approach to Understanding Acinetobacter baumannii Biofilm Formation and Drug Resistance , Jessie L. Allen

Cellular And Molecular Alterations Associated with Ovarian and Renal Cancer Pathophysiology , Ravneet Kaur Chhabra

Ecology and diversity of boletes of the southeastern United States , Arian Farid

CircREV1 Expression in Triple-Negative Breast Cancer , Meagan P. Horton

Microbial Dark Matter: Culturing the Uncultured in Search of Novel Chemotaxonomy , Sarah J. Kennedy

The Multifaceted Role of CCAR-1 in the Alternative Splicing and Germline Regulation in Caenorhabditis elegans , Doreen Ikhuva Lugano

Unraveling the Role of Novel G5 Peptidase Family Proteins in Virulence and Cell Envelope Biogenesis of Staphylococcus aureus , Stephanie M. Marroquin

Cytoplasmic Polyadenylation Element Binding Protein 2 Alternative Splicing Regulates HIF1α During Chronic Hypoxia , Emily M. Mayo

Transcriptomic and Functional Investigation of Bacterial Biofilm Formation , Brooke R. Nemec

A Functional Characterization of the Omega (ω) subunit of RNA Polymerase in Staphylococcus aureus , Shrushti B. Patil

The Role Of Cpeb2 Alternative Splicing In TNBC Metastasis , Shaun C. Stevens

Screening Next-generation Fluorine-19 Probe and Preparation of Yeast-derived G Proteins for GPCR Conformation and Dynamics Study , Wenjie Zhao

Theses/Dissertations from 2020 2020

Understanding the Role of Cereblon in Hematopoiesis Through Structural and Functional Analyses , Afua Adutwumwa Akuffo

To Mid-cell and Beyond: Characterizing the Roles of GpsB and YpsA in Cell Division Regulation in Gram-positive Bacteria , Robert S. Brzozowski

Spatiotemporal Changes of Microbial Community Assemblages and Functions in the Subsurface , Madison C. Davis

New Mechanisms That Regulate DNA Double-Strand Break-Induced Gene Silencing and Genome Integrity , Dante Francis DeAscanis

Regulation of the Heat Shock Response and HSF-1 Nuclear Stress Bodies in C. elegans , Andrew Deonarine

New Mechanisms that Control FACT Histone Chaperone and Transcription-mediated Genome Stability , Angelo Vincenzo de Vivo Diaz

Targeting the ESKAPE Pathogens by Botanical and Microbial Approaches , Emily Dilandro

Succession in native groundwater microbial communities in response to effluent wastewater , Chelsea M. Dinon

Role of ceramide-1 phosphate in regulation of sphingolipid and eicosanoid metabolism in lung epithelial cells , Brittany A. Dudley

Allosteric Control of Proteins: New Methods and Mechanisms , Nalvi Duro

Microbial Community Structures in Three Bahamian Blue Holes , Meghan J. Gordon

A Novel Intramolecular Interaction in P53 , Fan He

The Impact of Myeloid-Mediated Co-Stimulation and Immunosuppression on the Anti-Tumor Efficacy of Adoptive T cell Therapy , Pasquale Patrick Innamarato

Investigating Mechanisms of Immune Suppression Secondary to an Inflammatory Microenvironment , Wendy Michelle Kandell

Posttranslational Modification and Protein Disorder Regulate Protein-Protein Interactions and DNA Binding Specificity of p53 , Robin Levy

Mechanistic and Translational Studies on Skeletal Malignancies , Jeremy McGuire

Novel Long Non-Coding RNA CDLINC Promotes NSCLC Progression , Christina J. Moss

Genome Maintenance Roles of Polycomb Transcriptional Repressors BMI1 and RNF2 , Anthony Richard Sanchez IV

The Ecology and Conservation of an Urban Karst Subterranean Estuary , Robert J. Scharping

Biological and Proteomic Characterization of Cornus officinalis on Human 1.1B4 Pancreatic β Cells: Exploring Use for T1D Interventional Application , Arielle E. Tawfik

Evaluation of Aging and Genetic Mutation Variants on Tauopathy , Amber M. Tetlow

Theses/Dissertations from 2019 2019

Investigating the Proteinaceous Regulome of the Acinetobacter baumannii , Leila G. Casella

Functional Characterization of the Ovarian Tumor Domain Deubiquitinating Enzyme 6B , Jasmin M. D'Andrea

Integrated Molecular Characterization of Lung Adenocarcinoma with Implications for Immunotherapy , Nicholas T. Gimbrone

The Role of Secreted Proteases in Regulating Disease Progression in Staphylococcus aureus , Brittney D. Gimza

Advanced Proteomic and Epigenetic Characterization of Ethanol-Induced Microglial Activation , Jennifer Guergues Guergues

Understanding immunometabolic and suppressive factors that impact cancer development , Rebecca Swearingen Hesterberg

Biochemical and Proteomic Approaches to Determine the Impact Level of Each Step of the Supply Chain on Tomato Fruit Quality , Robert T. Madden

Enhancing Immunotherapeutic Interventions for Treatment of Chronic Lymphocytic Leukemia , Kamira K. Maharaj

Characterization of the Autophagic-Iron Axis in the Pathophysiology of Endometriosis and Epithelial Ovarian Cancers , Stephanie Rockfield

Understanding the Influence of the Cancer Microenvironment on Metabolism and Metastasis , Shonagh Russell

Modeling of Interaction of Ions with Ether- and Ester-linked Phospholipids , Matthew W. Saunders

Novel Insights into the Multifaceted Roles of BLM in the Maintenance of Genome Stability , Vivek M. Shastri

Conserved glycine residues control transient helicity and disorder in the cold regulated protein, Cor15a , Oluwakemi Sowemimo

A Novel Cytokine Response Modulatory Function of MEK Inhibitors Mediates Therapeutic Efficacy , Mengyu Xie

Novel Strategies on Characterizing Biologically Specific Protein-protein Interaction Networks , Bi Zhao

Theses/Dissertations from 2018 2018

Characterization of the Transcriptional Elongation Factor ELL3 in B cells and Its Role in B-cell Lymphoma Proliferation and Survival , Lou-Ella M.m. Alexander

Identification of Regulatory miRNAs Associated with Ethanol-Induced Microglial Activation Using Integrated Proteomic and Transcriptomic Approaches , Brandi Jo Cook

Molecular Phylogenetics of Floridian Boletes , Arian Farid

MYC Distant Enhancers Underlie Ovarian Cancer Susceptibility at the 8q24.21 Locus , Anxhela Gjyshi Gustafson

Quantitative Proteomics to Support Translational Cancer Research , Melissa Hoffman

A Systems Chemical Biology Approach for Dissecting Differential Molecular Mechanisms of Action of Clinical Kinase Inhibitors in Lung Cancer , Natalia Junqueira Sumi

Investigating the Roles of Fucosylation and Calcium Signaling in Melanoma Invasion , Tyler S. Keeley

Synthesis, Oxidation, and Distribution of Polyphenols in Strawberry Fruit During Cold Storage , Katrina E. Kelly

Investigation of Alcohol-Induced Changes in Hepatic Histone Modifications Using Mass Spectrometry Based Proteomics , Crystina Leah Kriss

Off-Target Based Drug Repurposing Using Systems Pharmacology , Brent M. Kuenzi

Investigation of Anemarrhena asphodeloides and its Constituent Timosaponin-AIII as Novel, Naturally Derived Adjunctive Therapeutics for the Treatment of Advanced Pancreatic Cancer , Catherine B. MarElia

The Role of Phosphohistidine Phosphatase 1 in Ethanol-induced Liver Injury , Daniel Richard Martin

Theses/Dissertations from 2017 2017

Changing the Pathobiological Paradigm in Myelodysplastic Syndromes: The NLRP3 Inflammasome Drives the MDS Phenotype , Ashley Basiorka

Modeling of Dynamic Allostery in Proteins Enabled by Machine Learning , Mohsen Botlani-Esfahani

Uncovering Transcriptional Activators and Targets of HSF-1 in Caenorhabditis elegans , Jessica Brunquell

The Role of Sgs1 and Exo1 in the Maintenance of Genome Stability. , Lillian Campos-Doerfler

Mechanisms of IKBKE Activation in Cancer , Sridevi Challa

Discovering Antibacterial and Anti-Resistance Agents Targeting Multi-Drug Resistant ESKAPE Pathogens , Renee Fleeman

Functional Roles of Matrix Metalloproteinases in Bone Metastatic Prostate Cancer , Jeremy S. Frieling

Disorder Levels of c-Myb Transactivation Domain Regulate its Binding Affinity to the KIX Domain of CREB Binding Protein , Anusha Poosapati

Role of Heat Shock Transcription Factor 1 in Ovarian Cancer Epithelial-Mesenchymal Transition and Drug Sensitivity , Chase David Powell

Cell Division Regulation in Staphylococcus aureus , Catherine M. Spanoudis

A Novel Approach to the Discovery of Natural Products From Actinobacteria , Rahmy Tawfik

Non-classical regulators in Staphylococcus aureus , Andy Weiss

Theses/Dissertations from 2016 2016

In Vitro and In Vivo Antioxidant Capacity of Synthetic and Natural Polyphenolic Compounds Identified from Strawberry and Fruit Juices , Marvin Abountiolas

Quantitative Proteomic Investigation of Disease Models of Type 2 Diabetes , Mark Gabriel Athanason

CMG Helicase Assembly and Activation: Regulation by c-Myc through Chromatin Decondensation and Novel Therapeutic Avenues for Cancer Treatment , Victoria Bryant

Computational Modeling of Allosteric Stimulation of Nipah Virus Host Binding Protein , Priyanka Dutta

Cell Cycle Arrest by TGFß1 is Dependent on the Inhibition of CMG Helicase Assembly and Activation , Brook Samuel Nepon-Sixt

Gene Expression Profiling and the Role of HSF1 in Ovarian Cancer in 3D Spheroid Models , Trillitye Paullin

VDR-RIPK1 Interaction and its Implications in Cell Death and Cancer Intervention , Waise Quarni

Regulation of nAChRs and Stemness by Nicotine and E-cigarettes in NSCLC , Courtney Schaal

Targeting Histone Deacetylases in Melanoma and T-cells to Improve Cancer Immunotherapy , Andressa Sodre De Castro Laino

Nonreplicative DNA Helicases Involved in Maintaining Genome Stability , Salahuddin Syed

Theses/Dissertations from 2015 2015

Functional Analysis of the Ovarian Cancer Susceptibility Locus at 9p22.2 Reveals a Transcription Regulatory Network Mediated by BNC2 in Ovarian Cells , Melissa Buckley

Exploring the Pathogenic and Drug Resistance Mechanisms of Staphylococcus aureus , Whittney Burda

Regulation and Targeting of the FANCD2 Activation in DNA Repair , Valentina Celeste Caceres

Mass Spectrometry-Based Investigation of APP-Dependent Mechanisms in Neurodegeneration , Dale Chaput

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  • Mol Biol Evol
  • v.37(2); 2020 Feb

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Molecular Biology and Evolution of Cancer: From Discovery to Action

Jason a somarelli.

1 Department of Medicine, Duke University Medical Center, Durham, NC

2 Duke Cancer Institute, Duke University Medical Center, Durham, NC

Heather Gardner

3 Sackler School of Graduate Biomedical Sciences, Tufts University, Medford, MA

Vincent L Cannataro

4 Department of Biology, Emmanuel College, Boston, MA

Ella F Gunady

Amy m boddy.

5 Department of Anthropology, University of California, Santa Barbara, CA

Norman A Johnson

6 Department of Biology, University of Massachusetts, Amherst, MA

Jeffrey Nicholas Fisk

7 Department of Biostatistics, Yale School of Public Health, New Haven, CT

Stephen G Gaffney

Jeffrey h chuang.

8 The Jackson Laboratory for Genomic Medicine, Farmington, CT

Francesca D Ciccarelli

9 Cancer Systems Biology Laboratory, The Francis Crick Institute, London, United Kingdom

10 King’s College London, London, United Kingdom

Anna R Panchenko

11 Department of Pathology and Molecular Medicine, School of Medicine, Queen’s University, Kingston, ON, Canada

12 Ontario Institute of Cancer Research, Toronto, ON, Canada

Kate Megquier

13 Broad Institute, Massachusettes Institute of Technology and Harvard University

Sudhir Kumar

14 Institute for Genomics and Evolutionary Medicine, and Department of Biology, Temple University, Philadelphia, PA

Alex Dornburg

15 North Carolina Museum of Natural Sciences, Raleigh, NC

James DeGregori

16 Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO

Jeffrey P Townsend

17 Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT

18 Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT

Cancer progression is an evolutionary process. During this process, evolving cancer cell populations encounter restrictive ecological niches within the body, such as the primary tumor, circulatory system, and diverse metastatic sites. Efforts to prevent or delay cancer evolution—and progression—require a deep understanding of the underlying molecular evolutionary processes. Herein we discuss a suite of concepts and tools from evolutionary and ecological theory that can inform cancer biology in new and meaningful ways. We also highlight current challenges to applying these concepts, and propose ways in which incorporating these concepts could identify new therapeutic modes and vulnerabilities in cancer.

The vast majority of cancer-related deaths occur in the context of metastatic spread of therapy-resistant cell lineages; and the progression from normal tissue to a localized, treatment-responsive, metastatic, and therapy-resistant disease is fundamentally an evolutionary process ( Nowell 1976 ). During this process a diverse population of cancer cells is subject to selective forces encountered within the tissue ecology of the body. Restrictions on space ( Chkhaidze et al. 2019 ), nutrients ( Lyssiotis and Kimmelman 2017 ), oxygen ( Amend and Pienta 2015 ), and other microenvironmental factors all select on clonal molecular variants within the primary tumor. These microenvironmental conditions can also induce a migratory and invasive phenotype that promotes tumor cell dissemination ( Jung et al. 2015 ; Jolly et al. 2017 ) and subsequent metastatic diversification in novel environments (reviewed in Labelle and Hynes 2012 ). In addition to the environments encountered within the primary and metastatic niche, therapy also imposes an intense selective pressure on cancer cells, sometimes focused on individual genes or gene domains, and often leads to rapid emergence of therapy-resistant subclones ( Enriquez-Navas et al. 2016 ).

While the population diversity subject to selective forces is most often associated with genetic diversity ( Ku et al. 2017 ; Mu et al. 2017 ), other factors also can create phenotypic diversity within a cancer cell population. These factors include DNA and histone modification (S. Li et al. 2016), transcriptional ( Puram et al. 2017 ; Peng et al. 2019 ), and post-transcriptional regulation ( Shapiro et al. 2011 ; Jolly et al. 2016 ; Pradella et al. 2017 ), and transcriptional noise ( Han et al. 2016 ). Selection acts on phenotypes—not directly on genotypes—and the phenotype conferred by a genotype can be highly context-dependent. Thus, no matter the source of (epi)genetic and transcriptional diversity, it is the overall phenotypic behavior of the cell that determines its persistence and fate in a cell population. Critically important phenotypes of cancer have been categorized as “Cancer Hallmarks”: an assortment of phenotypic traits in common across nearly all cancers ( Hanahan and Weinberg 2000 , 2011 ). These hallmarks of cancer include genome instability and mutation, sustained proliferative signaling, evading growth suppressors, enabling replicative immortality, resisting cell death, inducing angiogenesis, deregulating cellular energetics, tumor-promoting inflammation, avoiding immune destruction, and activating invasion and metastasis ( Hanahan and Weinberg 2011 ).

An instructive parallel can be drawn between the convergent evolution in cancer phenotypes towards cancer hallmarks and the phenotypic convergence observed in cave-adapted fish ( Gatenby et al. 2011 ). The diversity of cave-adapted fish throughout the world is the result of dozens of independent evolutionary habitat transitions by lineages that span the teleost Tree of Life. Nevertheless, virtually all obligate cavefish species have converged upon similar phenotypic hallmarks that provide adaptive advantages in cave environments ( Gatenby et al. 2011 ), a pattern of convergence that is remarkable considering these fishes span divergences that in some cases exceed the origin of mammals ( Near et al. 2012 ). Like cavefish, many cancer types are extremely genetically diverse, but they also converge under intense selective pressure upon certain hallmarks that enable their survival.

The phenotypic convergence onto the hallmarks of cancer observed across cancer types can be associated with molecular convergence as well. Sequencing has revealed common driver mutations in the same oncogene or tumor suppressor across different cancers. Common mutations in the TP53 DNA binding domain, KRAS G12 and G13, and domains of EGFR and PIK3CA are enriched across both individual patients and multiple cancer types ( Bailey et al. 2018 ). Convergences such as these manifest as oncogenic hotspots and tumor suppressors with high mutation loads—molecular evidence of the intense but context-dependent selective pressures on cancer cell lineages within tissues and growing tumors ( Fortunato et al. 2017 ).

Integrating Evolutionary Paradigms into Cancer Research

Understanding cancer from the lens of evolutionary theory is essential to fully comprehend cancer’s behavior. Herein we present a perspective on cancer and evolution that resulted from discussion during our SMBE-sponsored satellite meeting on the molecular biology and evolution of cancer. We highlight below fields of study in which evolutionary biology and cancer research naturally intersect and present a summary of potential solutions to some of the most pressing questions related to cancer and evolution ( fig. 1 ).

An external file that holds a picture, illustration, etc.
Object name is msz242f1.jpg

Current challenges in understanding cancer proposed by attendees at the 2019 SMBE Satellite Conference on the Molecular Biology and Evolution of Cancer.

Cross-Species Analyses of Cancer Reveals New Insights

The study of naturally-occurring cancers across species provides a unique perspective on cancer biology ( Wong et al. 2019 ). The core clinical and molecular similarities between cancer across species have supported the longstanding use of animals with spontaneously-occurring cancers to better understand mechanistic drivers of tumors. In small animal patients, such as dogs, the similarities to humans in disease presentation, response to treatment, and the development of drug-resistance and metastasis provide an opportunity to interrogate points of therapeutic intervention and generate a thorough preclinical assessment of novel treatments.

To optimize future comparative efforts, significant energy has been placed in characterizing the genomic landscape of multiple canine cancers. Notably, while many canine cancers exhibit a similar genomic landscape to their human counterparts, novel features of the disease in dogs may also help explain some of the differences in behavior of these diseases between species. For example, recent characterization of the genomic landscape of osteosarcoma in pet dogs revealed a similar mutation burden and complex spectrum of structural aberrations to that recognized in pediatric human osteosarcoma. However, unique features of osteosarcoma in dogs, such as mutations in the epigenetic regulator, SETD2 , and deletions in DMD , the gene encoding dystrophin, may help explain the more aggressive disease biology recognized in canine osteosarcoma ( Perry et al. 2014 ; Sakthikumar et al. 2018 ; Gardner et al. 2019 ). These canine-specific molecular alterations may inform on the biology of aggressive disease or pinpoint a unique molecular subtype of aggressive human osteosarcoma. Additional examples of canine cancers with shared disease biology in people include diffuse large B-cell lymphoma and leukemias, urothelial carcinomas, and soft tissue sarcomas, among others. For example, whole-exome sequencing and RNA-sequencing of golden retrievers with hemangiosarcoma revealed similar aberrations in genes and signaling pathways (Megquier et al.). These efforts often leverage the extensive tracts of linkage disequilibrium within breeds of dogs—driven by selective inbreeding—to map molecular variants that predispose them to cancer ( Sutter et al. 2004 ; Lindblad-Toh et al. 2005 ; Ostrander and Wayne 2005 ).

Across mammalian species, incidences of cancer are highly heterogeneous. For example, while cancer is the most common cause of death in dogs over 10 years of age, with many cancers observed at a higher incidence in dogs compared with people, other mammals, such as naked mole rats and elephants, are recognized to have a lower incidence of cancer ( Tollis, Boddy, et al. 2017 ; Tollis, Schiffman, et al. 2017 ). Nevertheless, comparative investigations of cancer between species are still limited; however, emerging studies are shedding light on the mechanisms of cancer protection in some species. Investigations of elephant genomes revealed copy number gains in the tumor suppressor, TP53 , a discovery that has since guided comparative research efforts to interrogate the role of tumor suppressor genes ( Abegglen et al. 2015 ; Sulak et al. 2016 ). Additionally, animals living under protected conditions (e.g., humans, domesticated, zoo/aquarium, and laboratory animals) represent a potential boon of model systems to investigators. These animals are far more likely to reach ages where cancers are much more common and in some cases can also experience modern exposures (e.g., cigarette smoking) that enhance cancer risk ( Hochberg and Noble 2017 ). By leveraging the unique features of cancer across multiple species, we have an unprecedented opportunity to advance future comparative and translational research efforts, thereby improving both our understanding of cancer biology and clinical outcomes for all patients.

Phylogenetic Evolution of Tumor Progression and Metastasis

Given the fundamental importance of evolutionary paradigms in cancer, tools, and concepts designed to study evolutionary relationships ( Darriba et al. 2018 ) are well suited to studies of cancer evolution ( Somarelli et al. 2017 ). For example, incorporating molecular phylogenetic frameworks has led to improvements in imputation of missing base calls in single-cell sequencing data ( Miura, Huuki, et al. 2018 ), and prediction of subclonal architecture from bulk sequencing data ( Fischer et al. 2014 ; Miura, Gomez, et al. 2018 ). Studies applying low-pass whole-genome sequencing to circulating tumor DNA have demonstrated the feasibility of applying phylogenetic tools and evolutionary principles to track clonal dynamics during the evolution of chemotherapy resistance ( Davidson et al. 2019 ). Whole-genome or whole-exome sequences can be used with slight modifications of classical methods of phylogenetic inference to reconstruct chronograms of cancer evolution ( Zhao et al. 2016 ). Furthermore, analysis of ancestral states can be highly informative regarding the sequence of events underlying tumorigenesis, metastasis, and the evolution of resistance. Superposition of these temporally granular investigations of the molecular evolution of cancer with patient clinical information provides tremendous insight into the biological and clinical time course of cancer, yielding patient-specific cancer histories and common trajectories of specific cancer types. Continued development of tools grounded in evolutionary principles, coupled with further innovations in sequencing technologies, may help stratify patients for clinical trials and/or identify new actionable targets for therapeutic intervention. One area with intense research activity has been the estimation of clonal history ( Beerenwinkel et al. 2015 ; Turajlic et al. 2015 ; Miura, Gomez, et al. 2018 ) and concomitant inference of selection ( Williams et al. 2016 , 2018 ; Tarabichi et al. 2018 ) using variant frequency data from tumor sequencing, an enterprise made especially challenging by cancer’s special molecular characteristics—clonal growth and competition, loss of heterozygosity, rampant copy number variation, and epigenetic effects. Extensive research is needed to adapt and develop molecular phylogenetic methods well suited for analyzing extensive tumor variation that can be much more complex than sequence variation in the analysis of natural populations and species.

Leveraging Evolutionary Fitness Landscapes in Cancer

Just as fitness represents the ability of an organism to survive and create genetically related offspring, it can also represent such competitive ability for cell lineages within an individual. Recognition of evolutionary selection as a metric of cancer driver genes’ relative importance led to the calculation of scaled selection coefficients as a means of ranking the effects of cancer drivers ( Cannataro, Gaffney, and Townsend 2018 ; Cannataro et al. 2019 ). However, the fitness of a phenotype conferred by these variants is determined not only just by their genotype, but also by resource availability ( Yun et al. 2009 ; Zapata et al. 2018 ; Bhandari et al. 2019 ) and epistatic interactions ( Wilkins et al. 2018 ; van de Haar et al. 2019 ). Therefore, fitness landscapes can shift when resource availability or the environment change to favor a subpopulation that is, by chance, better adapted to those new conditions. In the context of cancer, resources and environments are ever-changing. One key driver of this dynamic environment is age: inflammatory, metabolic, and mitochondrial functions change dramatically in older individuals ( Davizon-Castillo et al. 2019 ), and mutation accumulation with age is expected to drive declines in cell renewal potential in tissues, particularly those with high turnover ( Cannataro et al. 2016 ). These age-related changes in tissue architecture and function can alter the selective regime operating on stem or other progenitor cells. Henry et al. (2015) demonstrated that aging-associated increases in inflammation reduce the fitness of B-progenitor cells, promoting selection for progenitors with oncogenic mutations that restored their fitness, and leading to increased leukemias. As a malignancy expands, it creates additional microenvironmental hurdles that increase selection for adaptive genetic/phenotypic changes ( Gatenby and Gillies 2008 ), some of which engender specific cancer hallmarks. Therefore, studies of gene-by-environment regulation and evolution across tissue and tumor microenvironments could form a basis for novel approaches that reduce cancer initiation and progression.

Although changing environmental conditions clearly alter tissue and tumor fitness landscapes, the phenotypic plasticity of cancer cells can also provide cells with a fitness advantage. For example, using a zebrafish metastasis model of melanoma, Heilman et al. observed that disseminated melanoma cells were unpigmented, but the metastatic colonies became differentiated and gained pigmentation once colonies were established ( Gatenby and Gillies 2008 ; Heilmann et al. 2015 ). This observation is reminiscent of the epithelial–mesenchymal plasticity observed during metastatic dissemination and colonization in other solid tumors. For many epithelial-derived tumors, a subset of cells undergo a phenotypic transition from epithelial-like to mesenchymal-like. This epithelial–mesenchymal transition enables cells to migrate, invade, and disseminate; however, the increased invasive behavior as a mesenchymal-like cell comes at a cost: cells that have undergone epithelial–mesenchymal transition often slow or stop their proliferation through cell cycle arrest ( Vega et al. 2004 ; Mejlvang et al. 2007 ; Hu et al. 2008 ). Subsequent to seeding in a new environment, though, these mesenchymal-like cells can revert back to an epithelial-like phenotype, which reawakens proliferative capacity and enables cells to colonize ( Jolly et al. 2017 ). This phenotypic plasticity broadens the environmental conditions available to the cell and increases the cell’s overall fitness under varying resources and environments.

There are clear commonalities in fitness landscapes within and across individuals that have been demonstrated by the recurrent selection for a somewhat limited set of oncogenic mutations—particularly for the same cancer type—across many individuals. Intra-individual variability in the tissue microenvironment and phenotypic plasticity of individual cells make it challenging to discover how cancer lineages converge on fitness optima. Recurrent mutations often occur on the trunk of a clonal phylogenetic tree ( Zhao et al. 2016 ; Yates et al. 2017 ), indicating strong selection for a subset of oncogenic mutations early in cancer progression. This strong selection is also indicated by the association between the prevalence of observed mutations, the pathogenicity of those mutations, and the amplitude of mutations’ functional impacts on proteins and pathways (M. Li et al. 2016). To connect prevalence to the landscape of differential fitness effects of new mutations requires accounting for the natural variability in mutation rate at all scales throughout the genome and between different tissue types ( Cannataro, Gaffney, Stender, et al. 2018 ; Cannataro and Townsend 2018 , 2019 ; Brown et al. 2019 ). The relative heights of the peaks in the fitness landscape of tumorigenesis may be leveraged in a clinical setting—as the peaks of the fitness landscape correspond to relative increases in division and survival potential of cancer cells, and thus directly inform decision making about clinical trials ( Wilkins et al. 2018 ) and the potential for cancer cell adaptation to novel putative therapies ( Cannataro, Gaffney, Stender, et al. 2018 ).

Evolutionary Genomics of Cancer

Advances in sequencing technologies and analyses have continued to illuminate the dynamics of evolutionary processes in cancer. Exome sequencing revealed not only substantial inter-patient somatic genetic diversity with greater patient sampling ( Robinson et al. 2015 ; Armenia et al. 2018 ; Cannataro and Townsend 2019 ), but also remarkable intratumoral heterogeneity ( Gerlinger et al. 2012 ) that can be followed by disseminated metastatic diversity ( Zhao et al. 2016 ; Reiter et al. 2019 ). Subsequent studies have illustrated the evolutionary dynamics at play during the emergence of therapy resistance ( Gupta et al. 2017 ; Armstrong et al. 2019 ), as well as the role of nongenetic reprogramming of stromal compartments as contributors to therapy resistance ( Woolston et al. 2019 ). For example, Mourikis et al. (2019) used machine-learning to identify a series of “helper genes” that work together with cancer driver genes to promote esophageal cancer. These helper-driver networks converged toward the perturbation of molecular processes with well-known roles in cancer, such as intracellular signaling and cell cycle progression. The perturbation of similar processes is therefore recurrent in highly heterogeneous cancers, further supporting the importance of convergent evolution in cancer.

Discovery to Action: Adopting Evolutionary Approaches to Treat Cancer

From the selection of specific life history traits that protect organisms from cancer to the evolution of therapy-resistant and prometastatic disease states within a tumor, it is clear that the initiation, persistence, and progression of cancer is deeply rooted in molecular evolution. In exploring the connections between cancer and evolution, we asked how we can 1) use our understanding of molecular evolution to inform cancer discovery; 2) build molecular evolutionary models of cancer’s special characters; 3) better understand the relations between the hallmarks of cancer and cancer fitness landscapes; and 4) facilitate collaboration and communication between diverse areas of research ( fig. 1 ). Potential solutions to each of these challenges highlight the need for a more expansive toolkit to integrate established evolutionary paradigms into existing cancer research activities as well as communication across evolutionary and clinical disciplines.

Evolutionary and Ecological Paradigms Help Expand the Cancer Research Toolkit

A key concept underlying organismal evolution is the idea that environment shapes both phenotypes and the fitness values of phenotypes, leading to a fitness landscape. Likewise, cancer fitness landscapes can recapitulate and model the progression of cancer and the acquisition of its hallmarks. Application of fitness landscapes to cancer evolution requires an understanding of temporal changes in normal and cancerous tissues, in part because mutation order is a critical determinant of cancer evolution ( Zhao et al. 2016 ; Kent and Green 2017 ; Gomez et al. 2018 ) and fitness landscapes change with age ( Bilousova and DeGregori 2019 ; Guida et al. 2019 ; Nguyen et al. 2019 ; Rozhok and DeGregori 2019 ) and insult ( Roper et al. 2019 ). Multi-regional and temporal sampling and sequencing of tumors and cells will continue to be an essential resource, enabling comprehensive monitoring of the evolutionary process underlying cancer progression. Liquid biopsies, for example, provide a noninvasive method of periodically sampling the cancer genomes within a patient, including those from tumors located in multiple regions of the body ( Wan et al. 2017 ). Integration of longitudinal sampling with liquid biopsies, evolutionary genomics, and comparative oncology can be performed by leveraging other organisms when sampling from humans is challenging. Pet dogs acquire naturally occurring cancers; their of shorter lifespan enables time- and cost-effective data collection, and their cancers exhibit considerable biological similarity to those of their human counterparts ( Schiffman and Breen 2015 ). At the same time, multiple model systems that can reproducibly and quantitatively demonstrate intratumoral evolution in response to treatment: patient-derived xenografts can help distinguish patterns indicating selection from stochastic evolution across such multisample studies ( Kim et al. 2018 ). These paradigms from ecology and evolutionary biology may ultimately become essential to effective medical decision making.

Cross-Disciplinary Communication to Fuel Discovery and Innovation

Evolutionary paradigms are already well established for evolving populations of organisms and microorganisms. Because of the role of evolution in tumorigenesis, these paradigms are an invaluable resource for application to the better understanding of cancer origination, development, and biology. For example, metastasis can be studied through the lens of movement ecology, which describes how external pressures in an organism’s environment, combined with the organism’s intrinsic motivations and abilities, ultimately influence migration ( Amend et al. 2016 ). Fitness of neoplastic cells can be understood within the framework of life history theory, which suggests that limited resources necessitate tradeoffs in energy allocation to functions such as growth, maintenance, and reproduction ( Boddy et al. 2018 ). Conceptual parallels between organismal and cancer evolution suggest that phylogenetic methods and tools can be adapted to study cancer from a genetic and ecological perspective; cancer can likewise be exploited as a molecular model to better understand fundamental evolutionary paradigms. Increased connection and communication between evolutionary ecologists, cancer biologists, and clinicians has enormous potential to make a positive impact on our understanding of cancer and ultimately reveal novel approaches to help prolong and improve the lives of cancer patients.

Acknowledgment

This Perspective was developed with the assistance of funding from the Society of Molecular Biology and Evolution that supported the SMBE Satellite Meeting on the Molecular Biology and Evolution of Cancer at the Yale School of Public Health, April 12–13, 2019, organized by J.S. and J.P.T. Additional support was provided by the Notsew Orm Sands Foundation to J.P.T. and by a grant from the National Institutes of Health to S.K. ( {"type":"entrez-nucleotide","attrs":{"text":"LM012487","term_id":"686686571","term_text":"LM012487"}} LM012487 ).

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  • Journal of Molecular Biology Research
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JMBR: Call for Papers

Posted on Feb 16, 2023 We are now seeking submissions for Vol. 12, No. 1 2023 issue. Please submit your manuscript online or e-mail it to [email protected]. Please find the paper submission guide (MS-Word or PDF) and... Read More

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Posted on Oct 19, 2021 We are re-constructing our editorial board. All the editorial board members will receive a confirmation notice within a week. If you fail to receive the email, please contact me immediately. Read More

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Current: Vol. 12, No. 1 (2023)

  • Cytosol-Exposed Lysine Residues Affect the Cytosol-Membrane Distribution and Serine-129 Phosphorylation of Alpha-Synuclein
  •   Shiqing Lu    

molecular biology research papers pdf

  • Molecular Evaluation of HIV-1 HAART Efficacy, Comparison of TDF+3TC+EFV and AZT+3TC+NVP Regimens
  •   Babacar Faye    
  •   Mame Diarra Bousso Lam    
  •   Ismail Barkire    
  •   Micailou Magassouba    
  •   Cathy Cisse    
  •   Aissatou Ngom    
  •   Alioune Dieye    

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    The Journal of Molecular Cell Biology is a fully open access, ... Learn more. Call for Papers: Improving Women's Health ... Carcinogenesis DNA Research Molecular Human Reproduction Human Molecular Genetics International Immunology Food Quality and Safety Nucleic Acids Research Oxford Open Immunology Immunotherapy Advances Clinical and ...

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    Journal of Molecular Biology Research (JMBR) is an international, double-blind peer-reviewed, open-access journal, published by the Canadian Center of Science and Education. It publishes original research, applied, and educational articles in all areas of molecular biology. The journal is published in both print and online versions. The online version is free access and download.

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