ArticleMolecular cancer2020
RNA demethylase ALKBH5 prevents pancreatic cancer progression by posttranscriptional activation of PER1 in an m6A-YTHDF2-dependent manner.
Article in Molecular cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 248 papers, 2 of them syntheses that pooled it.
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Who cites it
248 citing papers in PubMed, 2 syntheses or guidelines pooled it, 430 citations in OpenAlex.
- Prognostic and clinicopathological value of m6A regulators in human cancers: a meta-analysis.Aging · 2022Pooled it
- Role of N6-Methyladenosine Methylation Regulators in the Drug Therapy of Digestive System Tumours.Frontiers in pharmacology · 2022Pooled it
- 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
- The m6A/METTL3 modifies USP11 to promote Warburg effect progression of colon cancer undifferentiated by HIF-1α/YAP signaling pathway.Translational cancer research · 2026Article
- GPSM2 Promotes Pancreatic Cancer Progression Through METTL3-Mediated m6A Modification of YAP1 mRNA.Journal of cellular and molecular medicine · 2026Article
- The crucial role of m6A methylation modification in nasopharyngeal carcinoma.Discover oncology · 2026Review
- Icariin suppresses glycolysis in prostate cancer by upregulating ALKBH5 to mediate EARS2 mJournal of molecular histology · 2026Article
- YTHDF1/SLC39A4 signaling axis promotes gastric cancer cell proliferation by suppressing cuproptosis ex vivo and in vitro.Cancer gene therapy · 2026Article
- Interplay of RNA mFASEB bioAdvances · 2026Article
- The RNA methylation modification as an immunometabolic regulatory hub in pancreatic cancer: from mechanistic insights to clinical translation perspectives.Molecular cancer · 2026Review
- ALKBH5/IGF2BP1-mediated mCell biology and toxicology · 2026Article
- ALKBH5 promotes ovarian cancer progression by activating Notch2 signaling.Biological procedures online · 2026Article
- ALKBH5 Accelerates the Progression of Head and Neck Squamous Cell Carcinoma by Decreasing Methylation of the lncRNA NEAT1.Applied biochemistry and biotechnology · 2026Article
- Emerging Dual Roles of ALKBH5 in Ischemia-reperfusion Injury: Mechanisms and Therapeutic Implications.Cell biochemistry and biophysics · 2026Review
- Identification and validation of PANoptosis-related genes in ankylosing spondylitis.BMC medical genomics · 2026Article
- Comprehensive analysis of m6A RNA methylation regulators for prognostic risk stratification and immune microenvironment characterization in colorectal cancer.Open medicine (Warsaw, Poland) · 2026Article
- Context-dependent functions of ALKBH5: a mechanistic framework linking cellular stress responses, immune regulation, viral infection, and therapeutic vulnerabilities.Frontiers in immunology · 2026Review
- Tamoxifen differentially modulates endometrial hyperplasia via wild-type and mutant p53 regulation of the ALKBH5-REG1A axis.Frontiers in oncology · 2026Article
- Differences in the expression profiles of m6A-related genes and the prognostic role in immunotherapy for lung adenocarcinoma patients.Frontiers in oncology · 2026Article
188 more citing papers are in PubMed but not listed here.
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9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundN6-methyladenosine (m6A) is the most abundant reversible methylation modification of eukaryotic mRNA, and it plays vital roles in tumourigenesis. This study aimed to explore the role of the m6A demethylase ALKBH5 in pancreatic cancer (PC).
methodsThe expression of ALKBH5 and its clinicopathological impact were evaluated in PC cohorts. The effects of ALKBH5 on the biological characteristics of PC cells were investigated on the basis of gain-of-function and loss-of-function analyses. Subcutaneous and orthotopic models further uncovered the role of ALKBH5 in tumour growth. mRNA and m6A sequencing and assays of m6A methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) were performed to identify the targeted effect of ALKBH5 on PER1. P53-binding sites in the ALKBH5 promoter were investigated by ChIP and luciferase assays to reveal the interplay between ALKBH5 and PER1-activated ATM-CHK2-P53/CDC25C signalling.
resultsALKBH5 loss characterized the occurrence and poor clinicopathological manifestations in patients with PC. Overexpression of ALKBH5 reduced tumoural proliferative, migrative, invasive activities in vitro and ameliorated tumour growth in vivo, whereas ALKBH5 knockdown facilitated PC progression. Mechanistically, ALKBH5 posttranscriptionally activated PER1 by m6A demethylation in an m6A-YTHDF2-dependent manner. PER1 upregulation led to the reactivation of ATM-CHK2-P53/CDC25C signalling, which inhibited cell growth. P53-induced activation of ALKBH5 transcription acted as a feedback loop regulating the m6A modifications in PC.
conclusionALKBH5 serves as a PC suppressor by regulating the posttranscriptional activation of PER1 through m6A abolishment, which may highlight a demethylation-based approach for PC diagnosis and therapy.
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