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 γ 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.
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28 December 2012
Aberrant microRNA Expression in Radiation-Induced Rat Mammary Cancer: The Potential Role of miR-194 Overexpression in Cancer Cell Proliferation
Daisuke Iizuka,
Tatsuhiko Imaoka,
Mayumi Nishimura,
Hidehiko Kawai,
Fumio Suzuki,
Yoshiya Shimada
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Radiation Research
Vol. 179 • No. 2
February 2013
Vol. 179 • No. 2
February 2013