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

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 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.

• Authors: Daisuke Iizuka, Tatsuhiko Imaoka, Mayumi Nishimura, Hidehiko Kawai, Fumio Suzuki, Yoshiya Shimada
• Journal: Radiation research (Radiat Res) Vol. 179 Issue 2 Pg. 151-9 (Feb 2013) ISSN: 1938-5404 [Electronic] United States
• PMID: 23273170 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN194 microRNA, rat
• MicroRNAs

Topics

• Animals
• Cell Line, Tumor
• Cell Proliferation (radiation effects)
• Female
• Gene Expression Regulation, Neoplastic (radiation effects)
• Genes, Tumor Suppressor (radiation effects)
• Humans
• Mammary Neoplasms, Experimental (genetics, pathology)
• MicroRNAs (genetics)
• Neoplasms, Radiation-Induced (genetics, pathology)
• Rats
• Rats, Sprague-Dawley