Aberrant microRNA expression in radiation-induced rat mammary cancer: the potential role of miR-194 overexpression in cancer cell proliferation.
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ABSTRACT: 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.
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE34119 | GEO | 2013/01/07
SECONDARY ACCESSION(S): PRJNA149871
REPOSITORIES: GEO
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