Functional Mechanism of MicroRNA-25-3p in Hilar Cholangiocarcinoma Cell Proliferation and Migration Through Regulation of Dual Specificity Phosphatase 5

Autor: Wan Zhong, Shiyang Dong, Han Wang, Chao Pan, Shiyong Yang
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Investigative Surgery, Vol 36, Iss 1 (2023)
Druh dokumentu: article
ISSN: 0894-1939
1521-0553
08941939
DOI: 10.1080/08941939.2023.2202768
Popis: Objective Hilar cholangiocarcinoma (HCCA) is a highly aggressive biliary tract tumor. microRNAs (miRs) exert dual actions in various cancers. This paper seeks to expound on the functional mechanisms of miR-25-3p/dual specificity phosphatase 5 (DUSP5) in HCCA cell proliferation and migration. Methods HCCA-related data were downloaded from GEO database to screen out differentially-expressed genes. The potential target miR (miR-25-3p) and its expression in HCCA were analyzed on Starbase. The binding relation between miR-25-3p and DUSP5 was confirmed by dual-luciferase assay. Levels of miR-25-3p and DUSP5 in FRH-0201 cells and HIBEpics were determined by RT-qPCR and Western blot. miR-25-3p and DUSP5 levels were intervened with to explore their effects on FRH-0201 cells. The apoptosis, proliferation, migration, and invasion of FRH-0201 cells were evaluated by TUNEL, CCK8, scratch healing, and Transwell assays. Flow cytometry was conducted to assess FRH-0201 cell cycle. Levels of cell cycle-related proteins were determined by Western blot. Results DUSP5 was weakly-expressed and miR-25-3p was highly-expressed in HCCA samples and cells. miR-25-3p targeted DUSP5. miR-25-3p suppressed FRH-0201 cell apoptosis and increased cell proliferation, migration, and invasion. DUSP5 overexpression partially abrogated miR-25-3p overexpression-exerted effects on FRH-0201 cells. miR-25-3p stimulated G1/S phase transition of FRH-0201 cells by targeting DUSP5. Conclusion miR-25-3p regulated HCCA cell cycle and facilitated cell proliferation and migration by targeting DUSP5.
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