miR-520a-5p induces docetaxel resistance in prostate cancer cells by regulating aerobic glycolysis

Abstract:

Objective To explore the effects of miR-520a-5p on the proliferation and docetaxel resistance of prostate cancer cells and the potential mechanisms.Methods The expression levels of miR-520a-5p in prostate cancer cells（PC-3/DU145） and normal prostate epithelial cells（RWPE-1） were measured by RT-qPCR. Western blot was used to determine whether miR-520a-5p regulated the expression of the key glycolytic enzymes hexokinase 2（HK2） and phosphofructokinase（PFKM）. The effects of miR-520a-5p on the proliferation and docetaxel resistance of prostate cancer cells were determined using cell counting kit-8. Glucose consumption and lactic acid production in the culture supernatant were assessed by enzyme-linked immunosorbent assay. According to the transfection， all cells were divided into 4 groups： minic group，minic NC group，inhibitor group and inhibitor NC group.Results miR-520a-5p was significantly down-regulated in prostate cancer cells（P<0.001）. Compared with the mimic NC group，the mimic group showed significant decreases in the proliferative ability（P<0.001），half-maximal inhibitory concentration（IC₅₀） of docetaxel，glucose consumption level，and lactic acid production level（P<0.001） of PC-3 and DU145 prostate cancer cells. Compared with the inhibitor NC group，the inhibitor group showed significantly increased proliferative ability（P<0.001） and glucose consumption and lactic acid production levels（P<0.001） of PC-3 and DU145 prostate cancer cells. Starbase database analysis indicated that there were binding sites between miR-520a-5p and HK2 and PFKM. Western blot results showed that miR-520a-5p negatively regulated the expression of HK2 and PFKM. Inhibiting the glycolysis of prostate cancer cells by 2-DG could recover the effect of miR-520a-5p on the proliferative ability of prostate cancer.Conclusion The low expression of miR-520a-5p in prostate cancer may up-regulate the key glycolytic enzymes HK2 and PFKM to enhance aerobic glycolysis，thereby inducing resistance to docetaxel in prostate cancer cells.