ArticleSignal transduction and targeted therapy2021
HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation.
Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 258 papers, 1 of them a synthesis that pooled it.
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Who cites it
258 citing papers in PubMed, 1 synthesis or guideline pooled it, 368 citations in OpenAlex.
- Prognostic and clinicopathological value of m6A regulators in human cancers: a meta-analysis.Aging · 2022Pooled it
- NEK2 promotes trastuzumab resistance in gastric cancer through WTAP/YTHDF1-dependent m6A regulation of FN1.Molecular biology reports · 2026Article
- HIF1α-KLF4 signaling dictates extra-erythrocyte expression of hemoglobin conferring sorafenib resistance in hepatocellular carcinoma.Signal transduction and targeted therapy · 2026Article
- Hypoxia-induced mGenes & diseases · 2026Article
- METTL16 S-glutathionylation-triggered RNA mActa pharmacologica Sinica · 2026Article
- Inhibiting METTL3 synergizes with Notch blockade to treat ESCC by targeting cancer stemness via m6A-JAG2.Journal of gastroenterology · 2026Article
- RNA modifications as determinants of cancer cell death: from epitranscriptomic mechanisms to therapeutic targeting.Functional & integrative genomics · 2026Review
- m6A-Driven Pexophagy Triggers Placental Ferroptosis to Impair Fetal Growth Upon Environmental Stress.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The N6-methyladenosine Modified EphA10 Promotes Prostate Cancer Progression by Activating the ERK/AKT Pathway.Biochemical genetics · 2026Article
- CircRSF1 Promoted HepG2 Cell Proliferation, Migration and Invasion Depending on EIF4A3.Digestive diseases and sciences · 2026Article
- Bioinformatics screening identifies USP9X as a pathogenic gene underlying thyroid and breast cancer comorbidity.Journal of molecular histology · 2026Article
- RNA methylation in cell death: mechanisms and clinical applications.Molecular cancer · 2026Review
- Understanding how hypoxia contributes to liver cancer stem cells maintenance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- YTHDF3 Mediates the Occurrence and Development of Breast Cancer by Regulating Glycolysis Through the mTOR-HIF1α-LHDA Axis.Journal of cellular and molecular medicine · 2026Article
- YTHDF1/SLC39A4 signaling axis promotes gastric cancer cell proliferation by suppressing cuproptosis ex vivo and in vitro.Cancer gene therapy · 2026Article
- The RNA methylation modification as an immunometabolic regulatory hub in pancreatic cancer: from mechanistic insights to clinical translation perspectives.Molecular cancer · 2026Review
- The ATG14: multi-layer autophagy control and an emerging therapeutic target in cancer.Apoptosis : an international journal on programmed cell death · 2026Review
- N6-methyladenosine-mediated up-regulation of ARRB2 regulates intrahepatic cholangiocarcinoma malignant progression and pemigatinib resistance through MAPK and Hippo signaling pathways.Cell death & disease · 2026Article
- Noncanonical function of epigenetic reader YTHDF1 inhibits MASLD progression by maintaining peroxisomes and mitochondrial homeostasis.Experimental & molecular medicine · 2026Article
- Mechanisms and therapeutic potential of YTHDF readers: Linking epitranscriptomics to cancer.Journal of pharmaceutical analysis · 2026Review
198 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
N6-methyladenosine (m6A), and its reader protein YTHDF1, play a pivotal role in human tumorigenesis by affecting nearly every stage of RNA metabolism. Autophagy activation is one of the ways by which cancer cells survive hypoxia. However, the possible involvement of m6A modification of mRNA in hypoxia-induced autophagy was unexplored in human hepatocellular carcinoma (HCC). In this study, specific variations in YTHDF1 expression were detected in YTHDF1-overexpressing, -knockout, and -knockdown HCC cells, HCC organoids, and HCC patient-derived xenograft (PDX) murine models. YTHDF1 expression and hypoxia-induced autophagy were significantly correlated in vitro; significant overexpression of YTHDF1 in HCC tissues was associated with poor prognosis. Multivariate cox regression analysis identified YTHDF1 expression as an independent prognostic factor in patients with HCC. Multiple HCC models confirmed that YTHDF1 deficiency inhibited HCC autophagy, growth, and metastasis. Luciferase reporter assays and chromatin immunoprecipitation demonstrated that HIF-1α regulated YTHDF1 transcription by directly binding to its promoter region under hypoxia. The results of methylated RNA immunoprecipitation sequencing, proteomics, and polysome profiling indicated that YTHDF1 contributed to the translation of autophagy-related genes ATG2A and ATG14 by binding to m6A-modified ATG2A and ATG14 mRNA, thus facilitating autophagy and autophagy-related malignancy of HCC. Taken together, HIF-1α-induced YTHDF1 expression was associated with hypoxia-induced autophagy and autophagy-related HCC progression via promoting translation of autophagy-related genes ATG2A and ATG14 in a m6A-dependent manner. Our findings suggest that YTHDF1 is a potential prognostic biomarker and therapeutic target for patients with HCC.
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