METTL3-mediated m6A modification promotes chemoresistance of intrahepatic cholangiocarcinoma by up-regulating NRF2 to inhibit ferroptosis in cisplatin-resistant cells.
Xiaoping Zheng, Huiying Li, Jian Lin, Ping Li, Xuexi Yang, Zhumei Luo, Li Jin
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引用次数: 0
Abstract
This study explores the relationship between m6A modification and ferroptosis in intrahepatic cholangiocarcinoma (ICC) and its impact on cisplatin resistance. We established cisplatin-resistant cells. CCK-8 and Transwell assays were conducted to evaluate the effects of METTL3 on drug resistance, migration, and invasion. RT-qPCR and Western blotting were used to measure target gene expression and the effects of overexpression and suppression. RIP, luciferase reporter assay, and other experiments were utilized to investigate the interaction between METTL3 and NRF2. Additionally, rescue experiments were performed to confirm the role of the METTL3/NRF2 axis in tumor drug resistance. METTL3 was found to be highly expressed in cisplatin-resistant cells, enhancing m6A modification levels, stabilizing NRF2 mRNA, and increasing NRF2 protein expression to inhibit ferroptosis. These findings indicate that the METTL3/NRF2 axis inhibits ferroptosis in cisplatin-resistant cells, thereby promoting chemotherapy resistance in ICC. This provides a potential direction for future research and treatment of ICC.
期刊介绍：
The Journal of Chemotherapy is an international multidisciplinary journal committed to the rapid publication of high quality, peer-reviewed, original research on all aspects of antimicrobial and antitumor chemotherapy.
The Journal publishes original experimental and clinical research articles, state-of-the-art reviews, brief communications and letters on all aspects of chemotherapy, providing coverage of the pathogenesis, diagnosis, treatment, and control of infection, as well as the use of anticancer and immunomodulating drugs.
Specific areas of focus include, but are not limited to:
· Antibacterial, antiviral, antifungal, antiparasitic, and antiprotozoal agents;
· Anticancer classical and targeted chemotherapeutic agents, biological agents, hormonal drugs, immunomodulatory drugs, cell therapy and gene therapy;
· Pharmacokinetic and pharmacodynamic properties of antimicrobial and anticancer agents;
· The efficacy, safety and toxicology profiles of antimicrobial and anticancer drugs;
· Drug interactions in single or combined applications;
· Drug resistance to antimicrobial and anticancer drugs;
· Research and development of novel antimicrobial and anticancer drugs, including preclinical, translational and clinical research;
· Biomarkers of sensitivity and/or resistance for antimicrobial and anticancer drugs;
· Pharmacogenetics and pharmacogenomics;
· Precision medicine in infectious disease therapy and in cancer therapy;
· Pharmacoeconomics of antimicrobial and anticancer therapies and the implications to patients, health services, and the pharmaceutical industry.
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