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

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 upregulated in radiation-induced mammary cancer compared with spontaneous cancer and normal mammary tissue. The expression of miR-192 and miR-194 also was upregulated in human breast cancer cell lines compared with non-cancer 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 suggested to act as tumor suppressors in MCF-7 and T47D breast cancer cells. Thus, the induction of rat mammary cancer by radiation involves aberrant expression of miRNAs, which may favor cell proliferation. Overall design: We performed miRNA microarray analysis on mammary carcinomas in Sprague-Dawley rat to identify radiation-specific miRNA expression patterns compared with spontaneous mammary carcinomas and normal mammary tissues.