MicroRNA-142-3p inhibits cell proliferation and chemoresistance in ovarian cancer via targeting sirtuin 1

MicroRNA-142-3p 通过靶向 sirtuin 1 抑制卵巢癌细胞增殖和化学耐药性

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作者:Jianlian Gao, Nan Wu, Xiaohong Liu, Yuechong Xia, Ying Chen, Shaoru Li, Zhijian Deng

Abstract

MicroRNAs (miRs) serve promoting or suppressive roles in various human cancer types, including ovarian cancer; however, the role of miR-142-3p in ovarian cancer growth and chemoresistance has not previously been studied. In the present study, reverse transcription-quantitative polymerase chain reaction and western blotting were used to examine miR and protein expression levels. An MTT assay was used to examine cell proliferation. A luciferase reporter gene assay was used to clarify the target gene of miR-142-3p. The present study reported that miR-142-3p expression levels were significantly lower in ovarian cancer tissues and cell lines, when compared with those in adjacent tissues and the normal human ovarian epithelial cell line IOSE386, respectively. The reduced expression of miR-142-3p was significantly associated with poor cell differentiation. Ectopic expression of miR-142-3p significantly inhibited the proliferation of ovarian cancer cells and increased the sensitivity of SKOV3/DDP cells to cisplatin. Sirtuin 1 (SIRT1) was identified as a target gene of miR-142-3p; SIRT1 expression was negatively regulated by miR-142-3p in ovarian cancer cells. Further investigation demonstrated that SIRT1 reversed the suppressive effects of miR-142-3p on the proliferation and chemoresistance of ovarian cancer cells. In addition, SIRT1 was significantly upregulated in ovarian cancer. A negative correlation between the expression of SIRT1 and miR-142-3p in ovarian cancer tissues was also observed. In summary, the present study indicated that miR-142-3p inhibits the proliferation and chemoresistance of ovarian cancer cells by targeting SIRT1. This suggests that miR-142-3p may be a promising therapeutic candidate for the treatment of ovarian cancer.

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