ArticleJournal of experimental & clinical cancer research : CR2023
METTL3 promotes chemoresistance in small cell lung cancer by inducing mitophagy.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers, 2 of them syntheses that pooled it.
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Who cites it
160 citing papers in PubMed, 2 syntheses or guidelines pooled it, 219 citations in OpenAlex.
- The molecular mechanisms of mitochondrial dynamics and mitophagy and their complex association with cancer drug resistance.Journal of translational medicine · 2025Pooled it
- The relationship between the network of non-coding RNAs-molecular targets and N6-methyladenosine modification in tumors of urinary system.Cell death & disease · 2024Pooled it
- Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer.Annals of medicine · 2026Review
- Article
- SUMOylated Reptin maintains low intracellular ROS levels by activating mitophagy to drive gemcitabine resistance in gallbladder cancer.Cell death & disease · 2026Article
- METTL14-Mediated lncRNA MSTRG.292666.16 mInternational journal of molecular sciences · 2026Article
- METTL3 promotes proliferation and invasion and inhibits ferroptosis in hepatocellular carcinoma by mediating m6A methylation modification of NUPR1.Molecular and cellular biochemistry · 2026Article
- Article
- Inhibiting METTL3 synergizes with Notch blockade to treat ESCC by targeting cancer stemness via m6A-JAG2.Journal of gastroenterology · 2026Article
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- Article
- Mitochondrial quality control in health and disease: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- METTL3- and IGF2BP1-associated m6A regulation of FADS2 contributes to lipid droplet accumulation and malignant progression in non-small cell lung cancer.Translational cancer research · 2026Article
- RNA methylation in cell death: mechanisms and clinical applications.Molecular cancer · 2026Review
- Transcriptional and epigenetic regulation of autophagy: mechanisms, disease relevance and therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- METTL3 in esophageal cancer: Current insights into molecular mechanisms, subtype heterogeneity and targeted therapy prospects (Review).International journal of oncology · 2026Review
- The Role of NMedComm · 2026Review
- Emerging roles of RNA mInternational journal of oncology · 2026Review
- Review
- Deciphering the CAF‑LCN2 axis: Key to overcoming anti‑PD‑L1 immunotherapy resistance in lung cancer.International journal of molecular medicine · 2026Article
100 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundSmall cell lung cancer (SCLC) is the most aggressive subtype of lung cancer. Although most patients are initially sensitive to first-line combination chemotherapy with cisplatin and etoposide, chemotherapy drug resistance easily develops and quickly leads to tumour progression. Therefore, understanding the mechanisms of chemotherapy drug resistance and how to reverse it is key to improving the prognosis of patients with SCLC. Moreover, N6-methyladenosine (m6A) is the most abundant mRNA modification and is catalysed by the methyltransferase complex, in which methyltransferase-like 3 (METTL3) is the sole catalytic subunit.
methodsThe effects of METTL3 on chemoresistance in SCLC cells were determined using qRT-PCR, Western blotting, immunohistochemistry, cell counting kit (CCK-8) assays, flow cytometry, and tumorigenicity experiments. Methylated RNA immunoprecipitation sequencing (MeRIP-seq), MeRIP qPCR, immunofluorescence, and drug inhibitor experiments were performed to confirm the molecular mechanism of Decapping Protein 2 (DCP2), which is involved in the chemoresistance of SCLC.
resultsIn the present study, we found that METTL3 is a marker for poor SCLC prognosis, and it is highly expressed in chemoresistant SCLC cells. METTL3 promotes SCLC chemoresistance by positively regulating mitophagy. METTL3 induces m6A methylation of DCP2 and causes the degradation of DCP2, which promotes mitochondrial autophagy through the Pink1-Parkin pathway, leading to chemotherapy resistance. We also found that STM2457, a novel METTL3 inhibitor, can reverse SCLC chemoresistance.
conclusionsThe m6A methyltransferase METTL3 regulates Pink1-Parkin pathway-mediated mitophagy and mitochondrial damage in SCLC cells by targeting DCP2, thereby promoting chemotherapy resistance in patients with SCLC.
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Registered trials
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.