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.

journal_name

Radiat Res

journal_title

Radiation research

authors

Iizuka D,Imaoka T,Nishimura M,Kawai H,Suzuki F,Shimada Y

doi

10.1667/RR2927.1

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

151-9

issue

2

eissn

0033-7587

issn

1938-5404

journal_volume

179

pub_type

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