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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1474701

METTL3 affects the biological function of lung adenocarcinoma through the FGF2 PA3K/AKT axis /PI3K/AKT /mTOR pathway

Provisionally accepted
Shaoting Chen Shaoting Chen 1,2,3Xiuqing Shen Xiuqing Shen 3Pengju Cao Pengju Cao 3Shunqian Chen Shunqian Chen 3Rongxing Zhong Rongxing Zhong 1Yingping Cao Yingping Cao 4*
  • 1 Fujian Medical University, Fuzhou, Fujian Province, China
  • 2 The University of Texas Health Science Center at San Antonio, San Antonio, United States
  • 3 Fujian Provincial Hospital, Fuzhou, Fujian Province, China
  • 4 Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China

The final, formatted version of the article will be published soon.

    This study aims to investigate the role of the m6A regulatory factor METTL3 in LUAD. By examining the expression of METTL3 in LUAD and conducting cellular functional experiments, the biological functions of METTL3 were discussed. mRNA-seq and MeRIP-qPCR were used to identify downstream target genes and pathways. The expression level of METTL3 in LUAD is lower than that in the control group. The downregulation of METTL3 promoted the proliferation, migration, and invasion of LUAD cells, while overexpression of METTL3 results in the opposite effects. Furthermore, we found that FGF2 was negatively regulated by METTL3. Interestingly, iInhibiting FGF2 reversed the tumor-promoting effects caused by METTL3 downregulation in LUAD cells. Silencing METTL3 enhanced the stability of FGF2. Finally, silencing FGF2 deactivate the PI3K/AKT signaling pathway in LUAD. The reduction of METTL3 in LUAD plays a crucial role in the pathogenesis of LUAD by activating the PI3K/AKTsignaling pathway through FGF2, indicating that METTL3 could be a promising therapeutic target for LUAD. Silencing METTL3 enhanced the stability of FGF2 mRNA. Silencing FGF2 resulted in reduced activity of the PI3K/AKT/mTOR signaling pathway in METTL3 knockdown LUAD cells. In summary, our findings unveil an intricate signaling network involving METTL3/FGF2/PI3K/AKT/mTOR in LUAD and provide valuable insights into the molecular mechanisms underlying tumor progression, thus holding significant implications for targeted therapy and advancing LUAD research.

    Keywords: LUAD, METTL3, M6A, FGF2, PI3K - AKT

    Received: 20 Aug 2024; Accepted: 24 Sep 2024.

    Copyright: © 2024 Chen, Shen, Cao, Chen, Zhong and Cao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Yingping Cao, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.