Altered microRNA expression patterns in irradiated hematopoietic tissues suggest a sex-specific protective mechanism.
To investigate involvement of miRNAs in radiation responses we used microRNAome profiling to analyze the sex-specific response of radiation sensitive hematopoietic lymphoid tissues. We show that radiation exposure resulted in a significant and sex-specific deregulation of microRNA expression in murine spleen and thymus tissues. Among the regulated miRNAs, we found that changes in expression of miR-34a and miR-7 may be involved in important protective mechanisms counteracting radiation cytotoxicity. We observed a significant increase in the expression of tumor-suppressor miR-34a, paralleled by a decrease in the expression of its target oncogenes NOTCH1, MYC, E2F3 and cyclin D1. Additionally, we show that miR-7 targets the lymphoid-specific helicase LSH, a pivotal regulator of DNA methylation and genome stability. While miR-7 was significantly down-regulated LSH was significantly up-regulated. These cellular changes may constitute an attempt to counteract radiation-induced hypomethylation. Tissue specificity of miRNA responses and possible regulation of miRNA expression upon irradiation are discussed.
Ilnytskyy
Yaroslav
Y
Department of Biological Sciences, University of Lethbridge, Lethbridge, Alta, Canada.
Zemp
Franz J
FJ
Koturbash
Igor
I
Kovalchuk
Olga
O
D000818:Animals; D005260:Female; D015870:Gene Expression / Q000528:radiation effects*; D038041:Lymphopoiesis / Q000235:genetics / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000096:biosynthesis*; D012737:Sex Factors; D013154:Spleen / Q000378:metabolism / Q000528:radiation effects*; D013950:Thymus Gland / Q000378:metabolism / Q000528:radiation effects*; D014965:X-Rays
D035683:MicroRNAs