Abstract: Objective:To evaluate the effect of microRNA-221(miR-221) on the neuroendocrine(NE) differentiation and invasive function of prostate cancer cells.Methods:The expressions of 7 miRNAs in the cell lines of androgen-dependent carcinoma of prostate(LNCaP) and androgen-independent carcinoma of prostate(LNCaP-AI) were detected by Northern blotting.The LNCaP and LNCaP-AI cells cultured in androgen-depleted medium were transfected with different synthetic miR-221, and their invasive abilities were evaluated by a matrigel invasion assay;the cell growth was assessed by using the cell counting kit-8 cell proliferation assay at different time points;the expression of neuron-specific enolase and dishevelled-2 (DVL2)during NE differentiation and migration was respectively measured by quantificational real-time polymerase chain reaction and Western blot.Results:The miR-221 level was increased significantly in LNCaP-AI cell line when compared with LNCaP cell line.Overexpression of miR-221 in LNCaP cells significantly promoted neuron-specific enolase expression and accelerated NE differentiation;suppression of miR-221 expression improved the abilities of migration and invasion of LNCaP-AI cells;meanwhile, the DVL2 mRNA and protein levels were upregulated after the transfection of anti-miR-221 in LNCaP-AI cells(P<0.01).Conclusions:There is a significant difference in miR-221 expression between androgen-dependent prostate cancer and androgen-independent prostate cancer cells.MiR-221 contributes to the NE differentiation of LNCaP cells, which may be the reason of androgen-independence.MiR-221 may regulate the migration of LNCaP-AI cells through DVL2 in advanced prostate cancer.