LncRNA H19/miR-675 axis represses prostate cancer metastasis by targeting TGFBI

Abstract

Prostate cancer is a leading cause of cancer-related mortality in men worldwide and there is a lack of effective treatment options for advanced (metastatic) prostate cancer. Currently, limited knowledge is available concerning the role of long non-coding RNAs in prostate cancer metastasis. In this study, we found that long non-coding RNA H19 (H19) and H19-derived microRNA-675 (miR-675) were significantly downregulated in the metastatic prostate cancer cell line M12 compared with the non-metastatic prostate epithelial cell line P69. Upregulation of H19 in P69 and PC3 cells significantly increased the level of miR-675 and repressed cell migration; however, ectopic expression of H19 in M12 cells could not increase the level of miR-675 and therefore had no effect on cell migration. Furthermore, we found that the expression level of either H19 or miR-675 in P69 cells was negatively associated with the expression of transforming growth factor β induced protein (TGFBI), an extracellular matrix protein involved in cancer metastasis. Dual luciferase reporter assays showed that miR-675 directly bound with 3′UTR of TGFBI mRNA to repress its translation. Taken together, we show for the first time that the H19-miR-675 axis acts as a suppressor of prostate cancer metastasis, which may have possible diagnostic and therapeutic potential for advanced prostate cancer. In this study, we show long non-coding RNA H19 represses prostate cancer metastasis in a miR-675-dependent manner. We further identify miR-675 directly inhibits the expression of an ECM protein TGFBI, which is involved in migration of cancer cells. Our findings provide a novel understanding of the roles of H19/miR-675 in prostate cancer metastasis and the mechanisms involved. © 2014 FEBS.