ArticleCell death & disease2023
METTL3 enhances pancreatic ductal adenocarcinoma progression and gemcitabine resistance through modifying DDX23 mRNA N6 adenosine methylation.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 39 citations in OpenAlex.
- Ferroptosis Suppression by the MAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- IGF2BP2 Promotes Esophageal Squamous-Cell Carcinoma Progression with Potential Involvement of PI3K/AKT Signaling.Current issues in molecular biology · 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
- Pan-cancer analysis and breast cancer validation reveal DEAD-box helicase 23 as a crucial prognostic and immuno-biomarker.Scientific reports · 2026Article
- Mechanisms and therapeutic potential of YTHDF readers: Linking epitranscriptomics to cancer.Journal of pharmaceutical analysis · 2026Review
- METTL3/IGF2BP3 axis promotes gemcitabine resistance of pancreatic cancer cells through regulating USP33-mediated PAK1 deubiquitination and degradation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The Regulatory Role of mCells · 2026Review
- mFrontiers in cell and developmental biology · 2026Review
- Rewriting the RNA code: an mFrontiers in immunology · 2026Review
- USP25 deubiquitinates cytosolic METTL3 to impede glioma proliferation via an m6A-independent pathway.iScience · 2025Article
- Structural Characterization ofInternational journal of molecular sciences · 2025Article
- The role and mechanism of METTL3 in cancer: emerging insights into m6A methylation and therapeutic potential.European journal of medical research · 2025Review
- Targeting RNA adenosine editing and modification enzymes for RNA therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Role of m6A RNA methylation regulators in pancreatic cancer: interactions and potential implications.Cancer cell international · 2025Review
- Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance.Signal transduction and targeted therapy · 2025Review
- Recent Findings in N6-Methyladenosine Modification and Significance in Pancreatic Cancer.Cancer medicine · 2025Review
- METTL3 depletion blocks vesicular stomatitis virus replication in pancreatic cancer cells through the establishment of an intrinsic antiviral state.Journal of virology · 2025Article
- Abnormal changes in metabolites caused by mJournal of advanced research · 2025Review
- The m6A reader IGF2BP2 promotes pancreatic cancer progression through the m6A-SLC1A5-mTORC1 axis.Cancer cell international · 2025Article
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aim of the present study was to clarify the mechanism of how METTL3 regulated pancreatic ductal adenocarcinoma (PDAC) progression by m6A modification of its downstream target mRNA and signaling pathway. Immunoblotting and qRT-PCR assays was employed to determine the expression levels of METTL3. In situ fluorescence hybridization was conducted to localize the cellular distribution of METTL3 and DEAD-box helicase 23 (DDX23). CCK8, colony formation, EDU incorporation, TUNEL, wound healing and Transwell assays were carried out accordingly to study the viability, proliferation, apoptosis, and mobility of cells under different treatments in vitro. Xenograft and animal lung metastasis experiments were also conducted to study the functional role of METTL3 or DDX23 on tumor growth and lung metastasis in vivo. MeRIP-qPCR and bioinformatical analyses were used to obtain the potential direct targets of METTL3. It was shown that m6A methyltransferase METTL3 was upregulated in PDAC tissues with gemcitabine resistance, and its knockdown sensitized pancreatic cancer cells to chemotherapy. Furthermore, silencing METTL3 remarkably reduced pancreatic cancer cell proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, validation experiments confirmed that DDX23 mRNA was a direct target of METTL3 in YTHDF1-dependent manner. Additionally, DDX23 silence resulted in the suppression of pancreatic cancer cell malignancy and PIAK/Akt signaling inactivation. Strikingly, rescuse experiments demonstrated the inhibitive effects of METTL3 silence on cell phenotypes and gemcitabine resistance were partially reversed by forcibly expressed DDX23. In summary, METTL3 promotes PDAC progression and gemcitabine resistance by modifying DDX23 mRNA m6A methylation and enhancing PI3K/Akt signaling activation. Our findings establish a potential tumor promotive and chemo-resistant role for METTL3/DDX23 axis in PDAC.
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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.