Aberrant microRNA expression in radiation-induced rat mammary cancer: the potential role of miR-194 overexpression in cancer cell proliferation.

Aberrant expression of microRNAs (miRNAs) is frequently associated with a variety of cancers, including breast cancer. We and others have demonstrated that radiation-induced rat mammary cancer exhibits a characteristic gene expression profile and a random increase in aberrant DNA copy number; however, the role of aberrant miRNA expression is unclear. We performed a microarray analysis of frozen samples of eight mammary cancers induced by gamma irradiation (2 Gy), eight spontaneous mammary cancers and seven normal mammary samples. We found that a small set of miRNAs was characteristically overexpressed in radiation-induced cancer. Quantitative RT-PCR analysis confirmed that miR-135b, miR-192, miR-194 and miR-211 were significantly up-regulated in radiation-induced mammary cancer compared with spontaneous cancer and normal mammary tissue. The expression of miR-192 and miR-194 also was up-regulated in human breast cancer cell lines compared with noncancer cells. Manipulation of the miR-194 expression level using a synthetic inhibiting RNA produced a small but significant suppression of cell proliferation and upregulation in the expression of several genes that are thought to act as tumor suppressors in MCF-7 and T47D breast cancer cells. Our data suggest that the induction of rat mammary cancer by radiation involves aberrant expression of miRNAs, which may facilitate cell proliferation. (C) 2013 by Radiation Research Society