ArticleAmerican journal of human genetics2019
Systematic Functional Interrogation of Genes in GWAS Loci Identified ATF1 as a Key Driver in Colorectal Cancer Modulated by a Promoter-Enhancer Interaction.
Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Colorectal Cancer Risk Loci: Prognostic Factors for Clinical Outcomes? A Systematic Review and Meta-Analysis.Cancer reports (Hoboken, N.J.) · 2025Pooled it
- Pancreatic cancer: molecular pathogenesis and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Characterization of cis-regulatory elements and functional variants in colorectal cancer using epigenomics and CRISPRi screenings.Nature cancer · 2025Article
- Genetic Regulation of Alternative Polyadenylation Provides Novel Insights into Molecular Mechanisms Underlying Non-small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Massively parallel variant-to-function mapping determines functional regulatory variants of non-small cell lung cancer.Nature communications · 2025Article
- Research progress of colorectal cancer in genomic and transcriptomic at multi-level.Frontiers in genetics · 2025Review
- Systematic functional interrogation of genome-wide association studies locus 17p13.3 deciphered role and genetic control of FAM57A in colorectal cancer development.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- An atlas of genetic effects on cellular composition of the tumor microenvironment.Nature immunology · 2024Article
- Integrated systematic functional screen and fine-mapping decipher the role and genetic regulation of RPS19 in colorectal cancer development.Archives of toxicology · 2024Article
- Developing an optimal stratification model for colorectal cancer screening and reducing racial disparities in multi-center population-based studies.Genome medicine · 2024Article
- Genome-wide enhancer-gene regulatory maps link causal variants to target genes underlying human cancer risk.Nature communications · 2023Article
- HSPA12A was identified as a key driver in colorectal cancer GWAS loci 10q26.12 and modulated by an enhancer-promoter interaction.Archives of toxicology · 2023Article
- STAT3-Mediated Promoter-Enhancer Interaction Up-Regulates Inhibitor of DNA Binding 1 (International journal of molecular sciences · 2023Article
- ATF1 promotes the malignancy of lung adenocarcinoma cells by transcriptionally regulating ZNF143 expression.Acta biochimica et biophysica Sinica · 2023Article
- Review
- Emerging roles of activating transcription factor (ATF) family members in tumourigenesis and immunity: Implications in cancer immunotherapy.Genes & diseases · 2022Review
- 3D chromatin architecture and transcription regulation in cancer.Journal of hematology & oncology · 2022Review
- Mbd2 deficiency alleviates retinal cell apoptosisvia the miR-345-5p/Atf1 axis in high glucoseinjury and streptozotocin-induced diabetic mice.Molecular therapy. Nucleic acids · 2021Article
- NEDD4 triggers FOXA1 ubiquitination and promotes colon cancer progression under microRNA-340-5p suppression and ATF1 upregulation.RNA biology · 2021Article
- BRCA1/ATF1-Mediated Transactivation is Involved in Resistance to PARP Inhibitors and Cisplatin.Cancer research communications · 2021Article
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genome-wide association studies (GWASs) have identified approximately 100 colorectal cancer (CRC) risk loci. However, the causal genes in these loci have not been systematically interrogated. We conducted a high-throughput RNA-interference functional screen to identify the genes essential for proliferation in the CRC risk loci of Asian populations. We found that ATF1, located in the 12q13.12 region, functions as an oncogene that facilitates cell proliferation; ATF1 has the most significant effect of the identified genes and promotes CRC xenograft growth by affecting cell apoptosis. Next, by integrating a fine-mapping analysis, a two-stage affected-control study consisting of 6,213 affected individuals and 10,388 controls, and multipronged experiments, we elucidated that two risk variants, dbSNP: rs61926301 and dbSNP: rs7959129, that located in the ATF1 promoter and first intron, respectively, facilitate a promoter-enhancer interaction, mediated by the synergy of SP1 and GATA3, to upregulate ATF1 expression, thus synergistically predisposing to CRC risk (OR = 1.77, 95% CI = 1.42-2.21, p = 3.16 × 10
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