METTL3-mediated m6A modification promotes chemoresistance of intrahepatic cholangiocarcinoma by up-regulating NRF2 to inhibit ferroptosis in cisplatin-resistant cells
机构:[1]Wenzhou Med Univ, Pingyang Hosp, Dept Infect Dis, Wenzhou, Zhejiang, Peoples R China[2]Sichuan Univ, West China Hosp, Outpatient Dept, Chengdu, Sichuan, Peoples R China四川大学华西医院[3]Sichuan Canc Hosp & Inst, Dept Oncol Radiat, Chengdu 610041, Sichuan, Peoples R China四川省肿瘤医院[4]Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa 999078, Peoples R China[5]Macau Univ Sci & Technol, Sch Pharm, Taipa 999078, Peoples R China
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.
第一作者机构:[1]Wenzhou Med Univ, Pingyang Hosp, Dept Infect Dis, Wenzhou, Zhejiang, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[3]Sichuan Canc Hosp & Inst, Dept Oncol Radiat, Chengdu 610041, Sichuan, Peoples R China[4]Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa 999078, Peoples R China[5]Macau Univ Sci & Technol, Sch Pharm, Taipa 999078, Peoples R China
推荐引用方式(GB/T 7714):
Zheng Xiaoping,Li Huiying,Lin Jian,et al.METTL3-mediated m6A modification promotes chemoresistance of intrahepatic cholangiocarcinoma by up-regulating NRF2 to inhibit ferroptosis in cisplatin-resistant cells[J].JOURNAL OF CHEMOTHERAPY.2024,doi:10.1080/1120009X.2024.2421700.
APA:
Zheng, Xiaoping,Li, Huiying,Lin, Jian,Li, Ping,Yang, Xuexi...&Jin, Li.(2024).METTL3-mediated m6A modification promotes chemoresistance of intrahepatic cholangiocarcinoma by up-regulating NRF2 to inhibit ferroptosis in cisplatin-resistant cells.JOURNAL OF CHEMOTHERAPY,,
MLA:
Zheng, Xiaoping,et al."METTL3-mediated m6A modification promotes chemoresistance of intrahepatic cholangiocarcinoma by up-regulating NRF2 to inhibit ferroptosis in cisplatin-resistant cells".JOURNAL OF CHEMOTHERAPY .(2024)