Purpose: Prostate cancer is an epithelial malignancy that occurs in the prostate and metastasis is a challenge of the treatment of prostate cancer. MicroRNA (miR)-19a was usually upregulated in several cancers at the roles of miR-19a in the metastasis in prostate cancer are still unclear.
Methods: A normal prostate epithelial cell line P69 and two prostate cancer cell lines PC3 and DU145 were used in this study. The mRNA levels of miR-19a and CUL5 were measured using qRT-PCR assay. Transwell and Western blot assays were conducted to calculate cell metastasis and epithelial-mesenchymal transition (EMT) properties in PC3 cells. Luciferase reporter assay was applied to validate that miR-19a targeted to CUL5.
Results: The expression of miR-19a was high in prostate cancer and its overexpression predicted poor outcome of prostate cancer patients. miR-19a regulated the expression of CUL5 by directly targeting its mRNA 3'-UTR in PC3 cells. The expression of CUL5 was lower in prostate cancer tissues and cell lines than in non-tumor tissues and normal cells. Downregulation of CUL5 predicted worse outcome of prostate cancer patients. miR-19a promoted cell migration, invasion and EMT in prostate cancer by directly binding to CUL5 mRNA 3'-UTR. CUL5 partially reversed the roles of miR-19a on the metastasis in prostate cancer.
Conclusion: miR-19a promoted migratory, invasive and EMT abilities by binding to CUL5 in prostate cancer. The newly identified miR-19a/CUL5 axis provides novel insight into the pathogenesis of prostate cancer.