Abstract 4069: The p47 Phox mediated redox-signal promotes myogenesis via p38 MAPK regulated microRNA-206

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC miR-206 is reported that one of the skeletal muscle specific myogenic factors which are halt the cell cycle via inhibition of DNA polymerase-alpha. So far, MyoD and AP1 are as well as known for miR-206 transcription factors. In this study, we take the evidence of another transcription factor MEF-2 which have a capacity for miR-206 expression in myogenesis. In addition, a novel miR-206 transcription factor is belonging to p38 MAPK activities that can be regulated by p47 Phox mediated redox-signal. It is hypothesis for a novel role of myogenic miR-206 regulation that p47 Phox generated redox-signal contributes to skeletal muscle differentiation via p38 MAPK activated miR-206. Followed the hypothesis, we were analysis the miR-206 promoter region (>-2k) by MatInspector (Promotor analysis tool, www.genomatix.de) for found out another plausible transcription factors and compare the miR-206 expression levels in SB203580 (p38 MAPK inhibitor), DPI (p47 Phox inhibitor) treated and differentiation condition by real-time PCR. Then, measuring the differentiation induced ROS during myogenesis by FACS. Moreover, we analyzed the expressions of myogenic factors and cell cycle involved molecules, including DNA polymerase-alpha, with immunoblotting. As a result, we hunt out a specious myogenic transcription factor MEF-2 that was not reported as a miR-206 expression factor. Both MEF-2 upstream activator p38 MAPK and p38 MAPK stimulating redox generator p47 Phox inhibition were accompanied with miR-206 down regulation. Besides, hindering of p38 MAPK and p47 Phox observed restoration of DNA polymerase-alpha transcription/translation levels in myogenic condition. Accordingly, we suggest that ROS activated p38 MAPK down-stream transcription factor MEF-2 may showed to a novel regulation factor of miR-206 in mouse skeletal muscle myogenesis. Key words: microRNA-206(miR-206), p47 Phox, p38 MAPK, MEF-2 Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4069.