ArticleAmerican journal of human genetics2016
Integrative Functional Genomics Implicates EPB41 Dysregulation in Hepatocellular Carcinoma Risk.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Genetic landscape of congenital pouch colon: systematic review and functional enrichment study.Pediatric surgery international · 2024Pooled it
- CHST9 rs1436904 genetic variant contributes to prognosis of triple-negative breast cancer.Scientific reports · 2017Trial
- Identification and validation of prognostic genes associated with M2 macrophage and heme metabolism in lung adenocarcinoma through bulk and single-cell RNA sequencing analysis.Discover oncology · 2026Article
- Micromapping (μMap) of HER2 Across Human Breast Cancers: Photocatalytic Proximity Labeling Identifies Primary Resistance Mechanisms and Functional Interactors.bioRxiv : the preprint server for biology · 2025Article
- PKR associates with 4.1R to promote anchorage-independent growth of hepatocellular carcinoma and lead to poor prognosis.Scientific reports · 2024Article
- [Effect of deletion of protein 4.1R on proliferation, apoptosis and glycolysis of hepatocyte HL-7702 cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Unraveling epigenomic signatures and effectiveness of electroconvulsive therapy in treatment-resistant depression patients: a prospective longitudinal study.Clinical epigenetics · 2024Article
- Genome-wide functional integration identified MAZ-controlled RPS14 dysregulation in hepatocellular carcinoma.Archives of toxicology · 2024Article
- Cytoskeletal Protein 4.1R in Health and Diseases.Biomolecules · 2024Review
- The role of hepatitis B virus genome variations in HBV-related HCC: effects on host signaling pathways.Frontiers in microbiology · 2023Review
- NClinical and translational medicine · 2022Article
- Transcriptomic profiling of Indian breast cancer patients revealed subtype-specific mRNA and lncRNA signatures.Frontiers in genetics · 2022Article
- LncRNA H19 modulated by miR-146b-3p/miR-1539-mediated allelic regulation in transarterial chemoembolization of hepatocellular carcinoma.Archives of toxicology · 2021Article
- METTL8 mRNA Methyltransferase Enhances Cancer Cell Migration via Direct Binding to ARID1A.International journal of molecular sciences · 2021Article
- N6-methyladenosine reader YTHDC2 and eraser FTO may determine hepatocellular carcinoma prognoses after transarterial chemoembolization.Archives of toxicology · 2021Article
- Circular RNA CircEPB41L2 Functions as Tumor Suppressor in Hepatocellular Carcinoma Through Sponging miR-590-5p.Cancer management and research · 2021Article
- Comprehensive analysis and establishment of a prediction model of alternative splicing events reveal the prognostic predictor and immune microenvironment signatures in triple negative breast cancer.Journal of translational medicine · 2020Article
- Silencing EPB41 Gene Expression Leads to Cell Cycle Arrest, Migration Inhibition, and Upregulation of Cell Surface Antigen in DC2.4 Cells.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- miR-608 and miR-4513 significantly contribute to the prognosis of lung adenocarcinoma treated with EGFR-TKIs.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- Identification of a Two-Gene (Frontiers in oncology · 2019Article
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genome-wide association studies (GWASs) have provided many insights into cancer genetics. However, the molecular mechanisms of many susceptibility SNPs defined by GWASs in cancer heritability and in promoting cancer risk remain elusive. New research strategies, including functional evaluations, are warranted to systematically explore truly causal genetic variants. In this study, we developed an integrative functional genomics methodology to identify cancer susceptibility SNPs in transcription factor-binding sites across the whole genome. Employing integration of functional genomic data from c-Myc cistromics, 1000 Genomes, and the TRANSFAC matrix, we successfully annotated 12 SNPs present in the c-Myc cistrome with properties consistent with modulating c-Myc binding affinity in hepatocellular carcinoma (HCC). After genotyping these 12 SNPs in 1,806 HBV-related HCC case subjects and 1,708 control subjects, we identified a HCC susceptibility SNP, rs157224G>T, in Chinese populations (T allele: odds ratio = 1.64, 95% confidence interval = 1.32-2.02; p = 5.2 × 10(-6)). This polymorphism leads to HCC predisposition through modifying c-Myc-mediated transcriptional regulation of EPB41, with the risk rs157224T allele showing significantly decreased gene expression. Based on cell proliferation, wound healing, and transwell assays as well as the mouse xenograft model, we identify EPB41 as a HCC susceptibility gene in vitro and in vivo. Consistent with this notion, we note that EPB41 expression is significantly decreased in HCC tissue specimens, especially in portal vein metastasis or intrahepatic metastasis, compared to normal tissues. Our results highlight the involvement of regulatory genetic variants in HCC and provide pathogenic insights of this malignancy via a genome-wide approach.
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