title: 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.affiliation: Department of Molecular Radiobiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Iizuka
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Imaoka
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nishimura
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Kawai
authors.forename: Fumio
authors.initials: F
authors.lastname: Suzuki
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Shimada
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D016147:Genes, Tumor Suppressor / Q000528:radiation effects; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D009381:Neoplasms, Radiation-Induced / Q000235:genetics* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C551975:MIRN194 microRNA, rat; D035683:MicroRNAs