Abstract 4158: MicroRNA-mediated regulation of Bmi1 expression in gastric and colon cancer cells.

Abstract

Abstract Background: MicroRNAs (miRs) target the 3’-untranslated region (3’-UTR) of mRNA and induce translational suppression or mRNA degradation. Bmi1 is a member of the polycomb-repressive complex 1 (PRC1) that has an essential role in maintaining chromatin silencing, and is involved in the self-renewal of neuronal, haematopoietic and intestinal cells through repression of the INK4A-ARF locus. The regulatory mechanism of Bmi1 in cancer cells is still unknown. The aim of this study is to clarify the miR-mediated regulatory mechanism of Bmi1 expression in gastric and colon cancer cells. Methods and Results: We searched for miRNAs that might regulate Bmi1 using miRBase and selected 64 miRNAs as a candidate. In these miRNAs, we focused miR-30e-3p that was known to be down-regulated in colon, breast and esophageal cancer cells. First, we examined the expression of miR-30e-3p in matched cancer tissue and non-tumor tissue using formalin-fixed paraffin-embedded(FFPE) samples of gastric and colon cancer. We confirmed the expression of miR-30e-3p was significantly lower in cancer tissue than in non-tumor tissue. Next, we measured the expression of miR-30e-3p and Bmi1 by real time PCR and western blotting using gastric and colon cancer cell lines. The endogenous expression of Bmi1 and miR-30e-3p showed inverse correlation in each cell lines. Then we examined the effect of overexpression or down regulation of miR-30e-3p on the expression of Bmi1. The suppression of miR-30e-3p increased Bmi1 expression, and the overexpression of miR-30e-3p decreased Bmi1 expression. Conclusion: Our current study revealed that the expression of Bmi1 was affected by miR-30e-3p in gastric and colon cancer. Mir-30e-3p may be a therapeutic target for the treatment of gastric and colon cancer. Citation Format: Hidetaka Sugihara, Takatsugu Ishimoto, Masayuki Watanabe, Hideo Baba. MicroRNA-mediated regulation of Bmi1 expression in gastric and colon cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4158. doi:10.1158/1538-7445.AM2013-4158