Bonci D et al. (2008) The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med 14: 1271–1277

The genes for the microRNAs miR-15a and miR-16-1 are located in the chromosomal region 13q14; deletions in this region are associated with prostate cancer progression. An Italian study has now shown that inhibition of miR-15a–miR-16-1 expression promotes prostate tumorigenesis, whereas restoration of miR-15a–miR-16-1 expression leads to tumor regression.

Bonci et al. constructed vectors that encoded antisense RNAs for miR-15a and miR-16-1; expression of the antisense RNAs led to sequestration of miR-15a and miR-16-1 and inhibition of their activity. In the noncancerous prostate cell line RWPE-1, infection with the vector conferred enhanced proliferation, survival and migration capacity, and, unlike control cells infected with a dummy virus, transformed RWPE-1 cells formed tumors in NOD–SCID mice. In addition, injection of specific antagomirs into prostates of BALB/c mice led to miR-15a–miR-16-1 downregulation and marked prostatic hyperplasia.

The researchers established that miR-15a and miR-16-1 targeted the expression of Bcl-2, Wnt3a and cyclin D1; the latter two proteins increased prostate cancer proliferation, while Wnt3a increased cell migration and, in synergy with Bcl-2, inhibited the activity of the cytotoxic drug docetaxel. Expression of these proteins increased when miR-15a and miR-16-1 were inactivated. In mice bearing miR-15a–miR-16-1-deficient prostate tumors, restoration of miR-15a–miR-16-1 activity by transfection with a virus led to considerable tumor shrinkage.

The authors conclude that miR-15a and miR-16-1 are tumor suppressor genes that act by controlling the activity of Wnt3a, Bcl-2 and cyclin D1. MicroRNA therapy might have future therapeutic potential against prostate cancer.