Abstract 131: Biological effect of miR-210 overexpression on renal carcinoma cells

Abstract

Abstract MiR-210 is significantly upregulated in clear cell renal cell carcinoma (CCC), but the mechanism and biological consequences of miR-210 upregulation are poorly understood. Here, we show that miR-210 is highly expressed in renal carcinoma cell lines and that its expression is clearly correlated with accumulation of hypoxia inducible factor 1α (HIF1α) under normoxia as well as hypoxia, suggesting that miR-210 upregulation in renal carcinoma cells is most likely due to accumulation of HIF1α. To reveal the effects of miR-210 upregulation, the miR-210 precursor was transfected into renal carcinoma cells. After transfection, the cells accumulated at G2/M phase of the cell cycle and their viability was decreased, suggesting that miR-210 overexpression may trigger an event that hinders normal cell division. Immunocytochemistry demonstrated a multipolar spindle accompanied by centrosome amplification in cells overexpressing miR-210. It has been reported that centrosome amplification induces chromosome mis-segregation, finally leading to chromosome instability and aneuploidy. Indeed, the proportion of aneuploid cells (>4n) was increased in miR-210 overexpressed cells. By using the TargetScan and PicTar algorithms, E2F3 was identified as one of the possible targets of miR-210, and was suppressed at the protein level by miR-210. Moreover, the proportion of aneuploid cells was increased in E2F3 siRNA transfected cells. On the basis of these results, we propose that miR-210 upregulation due to HIF1α accumulation may induce aneuploidy via E2F3 downregulation at least in part, and may play a role in tumorigenesis and/or progression of CCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 131. doi:10.1158/1538-7445.AM2011-131