METTL3 Drives Oral Cancer Progression via miR-146a-5p/SMAD4 Pathway | Oncotarget скачать в хорошем качестве

METTL3 Drives Oral Cancer Progression via miR-146a-5p/SMAD4 Pathway | Oncotarget

Oncotarget #published this #research paper on May 8, 2025, in Volume 16, entitled “METTL3 promotes oral squamous cell carcinoma by regulating miR-146a-5p/SMAD4 axis" by #researchers from the Laboratory of Molecular Medicine, Department of Biological Sciences, Birla Institute of Technology and Science, Pilani - Hyderabad Campus, Hyderabad 500078, India. ‪@BITSpilaniTechMedia‬ #cancer #oralcancer #oncology #paperspotlight #openaccess #openscience #peerreview #journal #publication #publishing #meded DOI - https://doi.org/10.18632/oncotarget.28717 Correspondence to - Piyush Khandelia - [email protected] Abstract N6-methyladenosine (m6A), one of the most prominent and reversible internal modifications of eukaryotic RNAs, has emerged as a critical regulator of gene expression in various cancers including oral squamous cell carcinoma (OSCC), wherein it shapes the tumor-specific epitranscriptomic gene-regulatory networks. METTL3, the primary m6A RNA methyltransferase, is significantly upregulated in OSCC cells leading to increased global m6A levels. Interestingly, METTL3 positively regulates miRNA biogenesis by modulating the processing of primary miRNAs in a m6A-dependent manner. We identified miR-146a-5p, an oncogenic miRNA as one of the METTL3-regulated miRNAs in OSCC. METTL3-depletion or inhibition of its catalytic activity leads to a reduction of miR-146a-5p and an appreciable accumulation of primary miR-146a in OSCC cells. Functional assays examining the effects of miR-146a-5p inhibition or overexpression confirm its oncogenic role in OSCC pathophysiology. Further, SMAD4, a central transducer in TGF-β signaling, was identified as a miR-146a-5p target. In OSCC cells, SMAD4-depletion exacerbates the oncogenic traits, whereas its overexpression exerts the opposite effect. Additionally, METTL3-depletion dysregulates SMAD4-regulated genes suggesting its potential involvement in SMAD4-dependent TGF-β signaling. Taken together, we report that METTL3, an oncogene regulates the expression of SMAD4, a tumor-suppressor via miR-146a-5p, thus unveiling a novel regulatory axis of METTL3/miR-146a-5p/SMAD4 in OSCC, which can potentially have therapeutic implications. Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/e... Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, oral cancer, m6A RNA methylation, METTL3, miR-146a-5p, SMAD4 About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube -    / @oncotargetjournal   LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJz... Media Contact [email protected] 18009220957