ArticleOncogene2023
m6A methylation regulates hypoxia-induced pancreatic cancer glycolytic metabolism through ALKBH5-HDAC4-HIF1α positive feedback loop.
Article in Oncogene, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 53 citations in OpenAlex.
- The role, regulatory mechanisms, and therapeutic implications of FTO in gastrointestinal cancer.Genes & diseases · 2026Review
- ALKBH5 in Cancer-Associated Fibroblasts Governs an Epitranscriptomic Axis That Drives Pancreatic Cancer Metastasis.Cancer research · 2026Article
- NChemical biology & drug design · 2026Article
- ALKBH5 activates creatine-driven thermogenesis by stabilizing CKB mRNA in response to cold.Nature metabolism · 2026Article
- RNA modifications as determinants of cancer cell death: from epitranscriptomic mechanisms to therapeutic targeting.Functional & integrative genomics · 2026Review
- Post-Translational Modifications in Pancreatic Cancer: Mechanisms to Clinical Applications.Journal of gastroenterology and hepatology · 2026Review
- Interplay between N6-methyladenosine RNA methylation and protein lactylation: a novel crosstalk linking metabolism and epigenetic regulation in human diseases.Journal of translational medicine · 2026Review
- Succinate drives breast cancer bone metastasis by activating the HIF1α/YTHDF1/YAP signaling axis to upregulate chemokine CXCL5 and disrupt the bone microenvironment.Apoptosis : an international journal on programmed cell death · 2026Article
- The Role of NMedComm · 2026Review
- The RNA methylation modification as an immunometabolic regulatory hub in pancreatic cancer: from mechanistic insights to clinical translation perspectives.Molecular cancer · 2026Review
- The N6-Methyladenosine RNA Demethylase AlkB Homolog 5 (ALKBH5) in Metabolic Diseases: Molecular Mechanisms and Pharmacological Implications-A Review.Biomolecules · 2026Review
- RMzyme: regulations of RNA-modifying enzymes in humans.Signal transduction and targeted therapy · 2026Article
- Phase separation and the tumor microenvironment.Cell communication and signaling : CCS · 2026Review
- Epitranscriptomic control of cancer hallmarks: Functions, mechanisms, and therapeutics of RNA modifications.Cancer cell · 2026Review
- METTL3-m6A-SLC25A11 Axis Promotes Chronic Hypoxia-Induced Cardiomyocyte Ferroptosis.Journal of the American Heart Association · 2026Article
- Plasma ALKBH5 depletion during severe intermittent hypoxia and its attenuation by galectin-3 inhibition: an experimental rat study.Frontiers in cardiovascular medicine · 2026Article
- RNA Methylation in Cancer Metabolism: from Mechanisms to Therapeutic Opportunities.International journal of biological sciences · 2026Review
- Post-transcriptional regulation of mRNA stability in pancreatic ductal adenocarcinoma.Frontiers in immunology · 2026Review
- Hypoxia-mediated mJournal of translational medicine · 2025Review
- Hypoxia-mediated regulation of mRNA metabolism: from transcription to stability.Cell communication and signaling : CCS · 2025Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic cancer (PC) is the most hypoxic cancer type among solid tumors. The dynamic changes of RNA N6-methyl-adenosine (m6A) contribute to tumor cells adaption to hypoxic microenvironmental. However, the regulatory mechanisms of hypoxia response in PC remains elusive. Here, we reported that the m6A demethylase ALKBH5 mediated a decrease of total mRNA m6A modification during hypoxia. Subsequently, methylated RNA immunoprecipitation sequencing (MeRIP-seq) combined with RNA sequencing (RNA-seq) revealed transcriptome-wide gene expression alteration and identified histone deacetylase type 4 (HDAC4) as a key target gene of m6A modification under hypoxic conditionds. Mechanistically, m6A methylation recognized by m6A reader-YTHDF2 enhanced the stability of HDAC4, and then promoted glycolytic metabolism and migration of PC cells. Our assays also demonstrated that hypoxia-induced HDAC4 enhanced HIF1a protein stability, and overexpressed HIF1a promoted transcription of ALKBH5 in hypoxic pancreatic cancer cells. Together, these results found a ALKBH5/HDAC4/HIF1α positive feedback loop for cellular response to hypoxia in pancreatic cancer. Our studies uncover the crosstalk between histone acetylation and RNA methylation modification on layer of epigenetic regulation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.