Xie Jianyun,Chen Weidong.miR-520a-5p induces docetaxel resistance in prostate cancer cells by regulating aerobic glycolysis[J].Journal of Chongqing Medical University,2023,48(8):909-915.
Xie Jianyun,Chen Weidong.miR-520a-5p induces docetaxel resistance in prostate cancer cells by regulating aerobic glycolysis[J].Journal of Chongqing Medical University,2023,48(8):909-915. DOI: 10.13406/j.cnki.cyxb.003314.
miR-520a-5p induces docetaxel resistance in prostate cancer cells by regulating aerobic glycolysis
To explore the effects of miR-520a-5p on the proliferation and docetaxel resistance of prostate cancer cells and the potential mechanisms.
Methods
2
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
2
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(IC
50
) 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
2
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.
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Keywords
references
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