Regulation of microRNA-21 for cisplatin resistance in Huh7 cells by PTEN and Wnt signaling pathways

Abstract

Abstract: Objective To investigate the mechanism of microRNAs in mediating cisplatin resistance in hepatocellular carcinoma (HCC).Methods MicroRNA-21 (miR-21) level was determined in HCC patients after cisplatin chemotherapy. miR-21 mimics and miR-21 inhibitor were used to upregulate or downregulate miR-21 level in Huh-7 cells. Human dickkopf-1(DKK-1) and bpV (phen) were used as Wnt inhibitor and phosphate and tension homology deleted on chromsome ten (PTEN) inhibitor, respectively. Relative mRNA level and protein expression were detected by real-time polymerase chain reaction (RT-PCR) and western blot, respectively. Results The results showed that overexpression of miR-21 decreased cisplatin (5 and 10 μg/mL)-induced inhibition of cell proliferation in Huh7 cells. Both mRNA level and protein expression of Wnt4 were elevated remarkably when Huh7 cells were treated with miR-21 mimics. Moreover, inhibition of Wnt4 and cell proliferation by DKK-1 was reversed using overexpression of miR-21. In addition, miR-21 mimics increased both mRNA level and protein expression of PTEN, and overexpression of miR-21 increased cell proliferation rate which was inhibited using bpV (phen, 100 and 200 nmol/L) in Huh7 cells. Conclusion miR-21 was involved in regulating resistance to cisplatin in Huh7 cells by activating Wnt and PTEN signaling pathways.

Key words: Hepatocellular carcinoma, Cisplatin, Chemoresistance, miR-21, Wnt, PTEN

LU Tian-fei, ZHONG Cheng-peng, GU Guang-xiang, HAO Jun, ZHANG Jian-jun , XU Ning. Regulation of microRNA-21 for cisplatin resistance in Huh7 cells by PTEN and Wnt signaling pathways[J]. Chinese Hepatolgy, 2018, 23(1): 31-36.

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