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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1464852
This article is part of the Research Topic The Molecular Mechanism in Anti-tumor Therapy Resistance View all 9 articles

Transcription factor MEF2D regulates aberrant expression of ACSL3 and enhances sorafenib resistance by inhibiting ferroptosis in HCC

Provisionally accepted
Xue Li Xue Li 1,2Shimin Chen Shimin Chen 1,2Yuanyuan Shi Yuanyuan Shi 3*Yuanjing Wang Yuanjing Wang 1,2*Qian Lin Qian Lin 2Wenshuo Fang Wenshuo Fang 4*Chao Wu Chao Wu 5*Leina Ma Leina Ma 2*
  • 1 College of Basic Medicine, Qingdao University, Qingdao, Shandong Province, China
  • 2 Qingdao Cancer Institute, Qingdao University, Qingdao, Shandong Province, China
  • 3 Biomedical center of Qingdao university, Qingdao, China
  • 4 Weifang Maternal and Child Health Hospital, Weifang, China
  • 5 Qingdao Central Hospital, Qingdao, Shandong Province, China

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

    Sorafenib is a first-line treatment for HCC; however, acquired resistance often results in a poor prognosis, indicating a need for more effective therapies. Sorafenib induces cell death through an iron-dependent mechanism known as ferroptosis, which is closely associated with the onset and progression of HCC. In this study, we observed that ACSL3 was aberrantly expressed in HCC and facilitated the progression from NAFLD to HCC. The abnormal expression of ACSL3 inhibited ferroptosis and enhanced sorafenib resistance in HCC. ACSL3-silenced HCC cells treated with specific concentrations of sorafenib exhibited reduced cell viability and increased levels of ferroptosis. The transcription factor MEF2D directly regulated the upregulation of ACSL3 expression. MEF2D bound to the promoter regions of ACSL3 to enhance its transcription and negatively regulate ferroptosis in HCC. In conclusion, our findings demonstrated for the first time that MEF2D regulated the aberrant expression of ACSL3 and enhanced sorafenib resistance by inhibiting ferroptosis in HCC. 1 Ethical Committee of the Medical College of Qingdao University (Animal Ethics Approval Number: QDU-AEC-2022097).Clinical information and surgical specimens were taken patients with NAFLD-related HCC from the

    Keywords: ACSL31, MEF2D2, HCC3, Ferroptosis4, sorafenib resistance5

    Received: 15 Jul 2024; Accepted: 21 Nov 2024.

    Copyright: © 2024 Li, Chen, Shi, Wang, Lin, Fang, Wu and Ma. 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:
    Yuanyuan Shi, Biomedical center of Qingdao university, Qingdao, China
    Yuanjing Wang, College of Basic Medicine, Qingdao University, Qingdao, 266071, Shandong Province, China
    Wenshuo Fang, Weifang Maternal and Child Health Hospital, Weifang, China
    Chao Wu, Qingdao Central Hospital, Qingdao, 266000, Shandong Province, China
    Leina Ma, Qingdao Cancer Institute, Qingdao University, Qingdao, Shandong 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.