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Merck

MicroRNA‑302a upregulation mediates chemo‑resistance in prostate cancer cells.

Molecular medicine reports (2019-04-04)
Yuqi Wu, Li Hu, Zizhen Qin, Xiangwei Wang
RESUMEN

MicroRNAs (miRNAs) are post‑transcriptional regulators that mediate the initiation and progression of human cancer. Growing evidence suggests that deregulation of miRNA expression levels underlies chemo‑resistance. To investigate whether miRNA‑302a (miR‑302a) is involved in mediating chemo‑resistance to paclitaxel in prostate cancer, a series of in vitro analyses were performed in paclitaxel‑resistant prostate cancer PC‑3PR cells and non‑resistant prostate cancer PC‑3 cells. It was demonstrated that the expression of miR‑302a was upregulated in PC‑3PR cells. Notably, ectopic expression of miR‑302a also increased resistance to paclitaxel in wild‑type PC‑3 cells. By contrast, silencing of miR‑302a in PC‑3PR cells sensitized the cells to paclitaxel. Gene and protein expression analyses suggested that the miR‑302a target gene breast cancer resistance protein (BCRP) may mediate chemo‑resistance to paclitaxel in PC‑3PR cells. In conclusion, the data suggested that elevated miR‑302a levels, in part, mediate sensitivity to paclitaxel in prostate cancer through the aberrant regulation of its downstream targets, AOF2, BCRP and permeability glycoprotein 1. These data have implications for the development of novel therapeutics in prostate cancer that may improve sensitivity to chemotherapeutics.