MiR-221 expression affects invasion potential of human prostate carcinoma cell lines by regulating DVL2

Abstract

Objectives To evaluate the effect of miR-221 on the neuroendocrine(NE) differentiation and invasive function of prostate cancer cells as a miRNA biomarker candidate for prostate cancer.Methods The expressions of 7 miRNAs in LNCaP,LNCaP-AI prostate cancer cell lines were detected by Northern blotting.LNCaP and LNCaP-AI cells cultured in androgen-depleted medium were transfected with different synthetic miRNAs.Their invasive abilities were evaluated by a matrigel invasion assay.Cell growth was assessed by using the CCK-8cell proliferation assay at different time points.The expression of neuron-specific enolase ( NSE ) and Dishevelled-2 (DVL2)during the neuroendocrine differentiation and migration respectively was measured by qRT-PCR and Western blot.Results The miR-221 level was significantly increased in androgen-independent prostate cancer (AIPC) cell line LNCaP-AI when compared with androgen -dependent prostate cancer (ADPC) cell line LNCaP.Overexpression of miR-221 in LNCaP cells significantly increased NSE expression and induced their NE differentiation.The suppression of miR-221 expression with anti-miR -221 increased the abilities of migration and invasion in LNCaP-AI cells.Meanwhile,the DVL2 mRNA and protein levels were upregulated after the transfection of anti -miR-221 in LNCaP-AI cells.Conclusions There is a significant difference in miR-221 expression between ADPC and AIPC cells.MiR-221 contributes to NE differentiation of ADPC cells,which may be the reason of androgen — independence.miR-221 may regulate the migration of AIPC cells through DVL2 as a key regulator in advanced prostate cancer. Key words: Prostate cancer Neoplasms; RNA