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.
Keywords: Beclin-1; autophagy; hepatocellular carcinoma; miR-101-3p; oxaliplatin.
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