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METTL3-mediated m6A modification promotes chemoresistance of intrahepatic cholangiocarcinoma by up-regulating NRF2 to inhibit ferroptosis in cisplatin-resistant cells

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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 [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
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关键词: METTL3 NRF2 cisplatin-resistance intrahepatic cholangiocarcinoma

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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.

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大类 | 4 区 医学
小类 | 4 区 传染病学 4 区 肿瘤学 4 区 药学
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最新[2023]版:
Q3 INFECTIOUS DISEASES Q3 ONCOLOGY Q3 PHARMACOLOGY & PHARMACY

影响因子: 最新[2023版] 最新五年平均 出版当年[2023版] 出版当年五年平均 出版前一年[2023版]

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第一作者机构: [1]Wenzhou Med Univ, Pingyang Hosp, Dept Infect Dis, Wenzhou, Zhejiang, Peoples R China
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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
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