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let‐7g sensitized liver cancer cells to 5‐fluorouracil by downregulating ABCC10 expression.
- Source :
-
Chemical Biology & Drug Design . Jan2024, Vol. 103 Issue 1, p1-10. 10p. - Publication Year :
- 2024
-
Abstract
- Patients with advanced liver cancer may benefit from 5‐fluorouracil (5‐FU) therapy. However, most of them eventually faced drug resistance, resulting in a poor prognosis. The present study aims to explore the potential mechanism of let‐7g/ABCC10 axis in the regulation of 5‐FU resistance in liver cancer cells. Huh‐7 cells were used to construct 5‐FU resistant Huh‐7/4X cells. CCK8, flow cytometry, and TUNEL staining were used to detect the characterization of Huh‐7 cells and Huh‐7/4X cells. Double luciferase report, PCR, and western blot analyses were used to detect the regulatory effects between let‐7g and ABCC10. The levels of biomarkers related to cell cycle progression and apoptosis were detected by western blot assays. The role of let‐7g in 5‐FU sensitivity of liver cancer cells was evaluated in nude mice. Compared with LX‐2 cells, the expression of let‐7g was decreased in Hep3B, HepG2, Huh‐7, and SK‐Hep1 cells, with the lowest expression in Huh‐7 cells. The sensitivity of Huh‐7 cell to 5‐FU was positively correlated with let‐7g expression. Transfection of let‐7g mimics inhibited the viability of Huh‐7/4X cells by prolonging the G1 phase, with the downregulation of ABCC10, PCNA, Cyclin D1, and CDK4. Meanwhile, let‐7g promoted apoptosis to increase 5‐FU sensitivity of Huh‐7/4X by downregulating ABCC10, Bcl‐XL as well as upregulating Bax, C‐caspase 3, and C‐PARP. Dual‐luciferase assay further confirmed that let‐7g inhibited ABCC10 expression by binding to the ABCC10 3'‐UTR region. Furthermore, let‐7g increased the sensitivity of Huh‐7/4X to 5‐FU in vitro and in vivo, which can be reversed by ABCC10 overexpression. In conclusion, let‐7g sensitized liver cancer cells to 5‐FU by downregulating ABCC10 expression. [ABSTRACT FROM AUTHOR]
- Subjects :
- *LIVER cells
*LIVER cancer
*CANCER cells
*WESTERN immunoblotting
*CANCER patients
Subjects
Details
- Language :
- English
- ISSN :
- 17470277
- Volume :
- 103
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Chemical Biology & Drug Design
- Publication Type :
- Academic Journal
- Accession number :
- 174845283
- Full Text :
- https://doi.org/10.1111/cbdd.14396