Prostate Cancer

H19[Host gene]

miR-675[miRNA]

TGFBI[mRNA]

Metastatic Prostate Cancer Cell Line M12

Homo sapiens (human)

Febs j 2014 Aug 281, 3766-75 doi:10.1111/febs.12902 PMID:24988946

lncRNA H19/MiR-675 axis represses prostate cancer metastasis by targeting TGFBI.

qRT-PCR;luciferase reporter assays

Prostate cancer (PCa) is a leading cause of cancer-related mortality in men worldwide and there is a lack of effective treatment options for advanced (metastatic) PCa. Currently, limited knowledge is available concerning the role of long noncoding RNAs (lncRNAs) in prostate cancer metastasis. In this study, we found that lncRNA H19 (H19) and H19-derived miR-675 were significantly down-regulated in the metastatic prostate cancer cell line M12 compared to the non-metastatic prostate epithelial cell line P69. Up-regulation of H19 in P69 & 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 b-induced protein (TGFBI), an ECM 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 H19/miR-675 axis acts as a suppressor of prostate cancer metastasis, which may have possible diagnostic and therapeutic potentials for advanced prostate cancer.