MiR-200b-3p elevates 5-FU sensitivity in cholangiocarcinoma cells via autophagy inhibition by targeting KLF4

Autor: Feng Peng, Ruizhi He, Yuhui Liu, Yu Xie, Guangbing Xiong, Xu Li, Min Wang, Chunle Zhao, Hang Zhang, Simiao Xu, Renyi Qin
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Non-coding RNA Research, Vol 9, Iss 4, Pp 1098-1110 (2024)
Druh dokumentu: article
ISSN: 2468-0540
DOI: 10.1016/j.ncrna.2024.06.004
Popis: Cholangiocarcinoma is one of the most lethal human cancers, and chemotherapy failure is a major cause of recurrence and poor prognosis. We previously demonstrated that miR-200 family members are downregulated in clinical samples of cholangiocarcinoma and inhibit cholangiocarcinoma tumorigenesis and metastasis. However, the role of differentially expressed miR-200b-3p in 5-fluorouracil chemosensitivity remains unclear. Here, we examined how miR-200b-3p modulates 5-fluorouracil chemosensitivity in cholangiocarcinoma. We observed that miR-200b-3p was associated with 5-fluorouracil sensitivity in cholangiocarcinoma and increased 5-fluorouracil-induced mitochondrial apoptosis in cholangiocarcinoma cells. Mechanistically, miR-200b-3p suppressed autophagy in cholangiocarcinoma cells to mediate 5-fluorouracil sensitivity. Further, we identified KLF4 as an essential target of miR-200b-3p in cholangiocarcinoma. Notably, the miR-200b-3p/KLF4/autophagy pathway augmented the chemosensitivity of cholangiocarcinoma cells to 5-fluorouracil. Our findings underscore the key role of miR-200b-3p in chemosensitivity to 5-fluorouracil and highlight the miR-200b-3p/KLF4/autophagy axis as a potential therapeutic target for cholangiocarcinoma.
Databáze: Directory of Open Access Journals