MicroRNA-381 suppresses proliferation and invasion of prostate cancer cells through downregulation of the androgen receptor

MicroRNA-381 通过下调雄激素受体抑制前列腺癌细胞的增殖和侵袭

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作者:Xin Rui, Ting-Ting Gu, Hua-Feng Pan, Si-Liang Shao, Hong-Xiang Shao

Abstract

Prostate cancer (PCa) is the most frequently diagnosed malignancy in men and its incidence has increased rapidly worldwide. Notably, the molecular mechanisms underlying prostate tumorigenesis have not been fully identified. The levels of microRNA (miR)-381 have been explored in numerous types of malignancy; however, the expression levels and biological function of miR-381 in PCa remain largely unknown. In the present study, reverse-transcription polymerase chain reaction was used to detect the expression levels of miR-381 in PCa cells and normal prostate epithelial cells. Subsequently, miR-381 antisense oligonucleotides and mimics were transfected into LNCaP PCa cells. Bioinformatics analysis was performed to identify the potential target genes of miR-381. Protein expression analysis, dual-luciferase reporter assay and a rescue assay were used to confirm the target of miR-381. The data suggested that the expression levels of miR-381 were significantly decreased in PCa cells compared with in normal prostatic epithelial cells. Furthermore, transfection of LNCaP cells with miR-381 mimics suppressed their proliferation, migration and invasion. In addition, bioinformatics analysis suggested that the androgen receptor (AR) was a target gene of miR-381. miR-381 suppressed the expression levels of AR by directly binding to its 3'-untranslated region. Furthermore, transfection with an AR plasmid partially attenuated miR-381-induced inhibition of cell proliferation, migration and invasion. The results of the present study suggested that miR-381 may act as a tumor suppressor in PCa by directly targeting the AR.

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