The role of miR-5094 as a proliferation suppressor during cellular radiation response via downregulating STAT5B

Abstract

MicroRNAs (miRNAs) play important roles in the regulation of cellular stress responses. We previously uncovered 10 novel human miRNAs which are induced by X-ray irradiation in HeLa cells using Solexa deep sequencing. The most highly expressed new miRNA, miR-5094, was predicted to target STAT5b. This study wonders whether miR-5094 participates in cellular radiation response via STAT5b. Firstly, direct interaction between miRNA-5094 and the STAT5b 3'-UTR was confirmed by luciferase reporter assay. Then, the radiation responsive expression of miR-5094 and STAT5b were measured in HeLa and Jurkat cells, and the expressions of down-stream genes of STAT5b after ionizing radiation (IR) were detected in HeLa cells. At last, the effects of miR-5094 on survival fraction, cell proliferation, cell cycle arrest and apoptosis induced by IR were investigated in HeLa cells, Jurkat cells and human peripheral blood T cells. It was found that up-regulation of miR-5094 by radiation induction or miRNA mimic transfection suppressed expression of STAT5b, and consequently decreased the transcription of down-stream Igf-1 and Bcl-2. Additionally, over expression of miR-5094 resulted in proliferation suppression and knockdown of miR-5094 by miRNA inhibitor after irradiation partially reversed the proliferation suppression induced by miR-5094 in HeLa cells, Jurkat cells and CD4+ T cells. Collectively, our findings demonstrate that up-regulation of miR-5094 down-regulated the expression of STAT5b, thereby suppressing cell proliferation after X-ray irradiation.