ArticleFrontiers in oncology2021
Stimulation of Let-7 Maturation by Metformin Improved the Response to Tyrosine Kinase Inhibitor Therapy in an m6A Dependent Manner.
Article in Frontiers in oncology, 2021. 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 21 papers.
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Who cites it
21 citing papers in PubMed, 51 citations in OpenAlex.
- The role of m6A modification in non-small cell lung cancer: functional insights and impact on therapy resistance.Cancer cell international · 2025Review
- MicroRNA chemical modifications in post-transcriptional gene silencing and human diseases.Molecular therapy. Nucleic acids · 2025Review
- The N6-methyladenosine-mediated cLMNB1 degrades FGFR4 to overcome osimertinib resistance in non-small cell lung cancer.Cell death & disease · 2025Article
- The epitranscriptome meets non-coding RNA: m6A-mediated regulation in oncogenesis and therapy.Frontiers in cell and developmental biology · 2025Review
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Refining the optimal CAF cluster marker for predicting TME-dependent survival expectancy and treatment benefits in NSCLC patients.Scientific reports · 2024Article
- Targeting non-coding RNAs to overcome osimertinib resistance inFrontiers in oncology · 2024Review
- The role of m6A methylation in targeted therapy resistance in lung cancer.American journal of cancer research · 2024Review
- Mechanisms of Regulation of the Expression of miRNAs and lncRNAs by Metformin in Ovarian Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Review
- The roles and implications of RNA mNature reviews. Clinical oncology · 2023Review
- Enhancement of TKI sensitivity in lung adenocarcinoma through m6A-dependent translational repression of Wnt signaling by circ-FBXW7.Molecular cancer · 2023Article
- The critical roles of m6A RNA methylation in lung cancer: from mechanism to prognosis and therapy.British journal of cancer · 2023Review
- Small RNA modifications: regulatory molecules and potential applications.Journal of hematology & oncology · 2023Review
- Metformin attenuates multiple myeloma cell proliferation and encourages apoptosis by suppressing METTL3-mediated m6A methylation of THRAP3, RBM25, and USP4.Cell cycle (Georgetown, Tex.) · 2023Article
- Emerging roles of m6A RNA modification in cancer therapeutic resistance.Experimental hematology & oncology · 2023Review
- The role of mFrontiers in endocrinology · 2023Review
- Emerging Mutual Regulatory Roles between mInternational journal of molecular sciences · 2023Review
- Recent Advances in RNA mCancer treatment and research · 2023Article
- Metformin and Cancer, an Ambiguanidous Relationship.Pharmaceuticals (Basel, Switzerland) · 2022Review
- HNRNPA2B1 Demonstrates Diagnostic and Prognostic Values Based on Pan-Cancer Analyses.Computational and mathematical methods in medicine · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular mechanism of the tyrosine kinase inhibitor (TKI) resistant lung adenocarcinoma is currently unclear, and the role of methylated adenosine at the N6 position in the resistance of cancer stem cells (CSCs) therapy is unknown. This study identified a novel and effective strategy to enhance TKIs therapy response. We first confirmed the sensitization of Metformin enforcing on Osimertinib treatment and revealed the mature miRNAs signatures of the Osimertinib resistant H1975 and HCC827 cells. Let-7b expression was stimulated when adding Metformin and then increasing the therapy sensitivity by decreasing the stem cell groups expanding. Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3a/b) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. We revealed that the maturation processing signaling stimulated the methylation regulation of the miRNAs, and may determine the stemness control of the therapy resistance. Our findings may open up future drug development, targeting this pathway for lung cancer patients.
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