Wenping Sun1, Qiang Zhang2, Zhiwei Wu3, Na Xue3. 1. Department of Abdominal Surgery, Gansu Provincial Cancer Hospital Lanzhou, Gansu, China. 2. Department of Urology, Gansu Provincial Cancer Hospital Lanzhou, Gansu, China. 3. College of Basic Medicine, Gansu University of Chinese Medicine Lanzhou, Gansu, China.
Abstract
BACKGROUND: Increasing evidence has shown that autophagy can contribute to drug resistance. Whether microRNA-101-3p (miR-101-3p) participates in oxaliplatin (OXA) resistance via modulating Beclin-1-mediated autophagy in hepatocellular carcinoma (HCC) has not been reported. METHODS: OXA-resistant Huh7 cells (Huh7/OXA) or HepG2 cells (HepG2/OXA) and OXA-sensitive Huh7 or HepG2 cells were treated with OXA in various concentrations. The expressions of miR-101-3p and Beclin-1 were monitored using qRT-PCR. Western blot was used to evaluate cell autophagy. Cell viability and the IC50 of OXA were determined using an MTT assay. Cell apoptosis was evaluated by flow cytometry. A luciferase reporter assay was introduced to confirm the relationship between miR-101-3p and Beclin-1. RESULTS: miR-101-3p was decreased in HCC resistant tissues and cells. Moreover, an increased expression of miR-101-3p reduced cell viability and the IC50 of OXA, and it promoted cell apoptosis in Huh7/OXA and HepG2/OXA cells. miR-101-3p negatively modulated the expression of Beclin-1. Interestingly, the overexpression of Beclin-1 receded the effect of the ectopic expression of miR-101-3p in OXA-resistant HCC cells. In OXA-sensitive Huh7 and HepG2 cells, OXA significantly increased the expressions of LC3 and Beclin-1, and it decreased the abundance of p62. Furthermore, OXA markedly blocked cell viability, which was exacerbated by the introduction of the autophagy inhibitor CQ. Additionally, the elevated expression of miR-101-3p suppressed cell autophagy by inhibiting the expression of LC3 and Beclin-1 and facilitating the expression of p62. CONCLUSION: miR-101-3p is responsible for the sensitivity of HCC cells to OXA by inhibiting Beclin-1-mediated autophagy. IJCEP
BACKGROUND: Increasing evidence has shown that autophagy can contribute to drug resistance. Whether microRNA-101-3p (miR-101-3p) participates in oxaliplatin (OXA) resistance via modulating Beclin-1-mediated autophagy in hepatocellular carcinoma (HCC) has not been reported. METHODS:OXA-resistant Huh7 cells (Huh7/OXA) or HepG2 cells (HepG2/OXA) and OXA-sensitive Huh7 or HepG2 cells were treated with OXA in various concentrations. The expressions of miR-101-3p and Beclin-1 were monitored using qRT-PCR. Western blot was used to evaluate cell autophagy. Cell viability and the IC50 of OXA were determined using an MTT assay. Cell apoptosis was evaluated by flow cytometry. A luciferase reporter assay was introduced to confirm the relationship between miR-101-3p and Beclin-1. RESULTS: miR-101-3p was decreased in HCC resistant tissues and cells. Moreover, an increased expression of miR-101-3p reduced cell viability and the IC50 of OXA, and it promoted cell apoptosis in Huh7/OXA and HepG2/OXA cells. miR-101-3p negatively modulated the expression of Beclin-1. Interestingly, the overexpression of Beclin-1 receded the effect of the ectopic expression of miR-101-3p in OXA-resistant HCC cells. In OXA-sensitive Huh7 and HepG2 cells, OXA significantly increased the expressions of LC3 and Beclin-1, and it decreased the abundance of p62. Furthermore, OXA markedly blocked cell viability, which was exacerbated by the introduction of the autophagy inhibitor CQ. Additionally, the elevated expression of miR-101-3p suppressed cell autophagy by inhibiting the expression of LC3 and Beclin-1 and facilitating the expression of p62. CONCLUSION: miR-101-3p is responsible for the sensitivity of HCC cells to OXA by inhibiting Beclin-1-mediated autophagy. IJCEP
Authors: Flavia Fondevila; Carolina Méndez-Blanco; Paula Fernández-Palanca; Tania Payo-Serafín; Jos van Pelt; Chris Verslype; Javier González-Gallego; José L Mauriz Journal: Int J Mol Sci Date: 2021-10-29 Impact factor: 5.923