Abstract 3081: Tristetraprolin Controls let-7 regulator-Lin28 mRNA stability

Abstract

Abstract The RNA binding protein tristetaprolin (TTP) regulates expression of many cancer-associated genes through binding to AU-rich elements (AREs) in the 3’ untranslated region (3’UTR) and facilitating rapid mRNA decay. In this study, we investigated the role of TTP in the control of micro RNA let-7 expression through regulation of Lin28 expression. TTP overexpression significantly suppressed the growth of PA1 human ovarian cancer cell line through down-regulation of CDC34 expression. However, CDC34 does not have the ARE motif within its 3’UTR, suggesting that TTP can not directly regulate CDC34 expression. Instead, CDC34 expression was regulated by let-7. Interestingly, we found that TTP regulates the expression of Lin28 which has been reported to be involved in maturation of let-7. Lin28 mRNA contains two AREs (ARE1 and ARE2) within the 3’UTR, and TTP destabilized a luciferase mRNA containing Lin28 ARE1 and directly bound to the ARE1 of Lin28 mRNA. These studies established Lin28 mRNA as a physiological target of TTP and demonstrate that TTP can control the expression levels of microRNA let-7 through regulation of Lin28 mRNA stability. 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 3081. doi:10.1158/1538-7445.AM2011-3081