Abstract 3082: Exploring LIN28 mRNA targets in breast cancer cells

Abstract

Abstract LIN28 is a RNA binding protein and a pluripotency factor. It represses tumor suppressing microRNA let-7 and thus derepresses let-7 oncogene targets such as HMGA2, K-Ras and c-Myc. In addition, LIN28 binds and enhances translation of IGF-2 mRNA a known mitogen. Recent reports show that LIN28 overexpression promotes tumor cell migration and cellular transformation through repression of let-7, and that overexpression is associated with advanced stages of disease, including breast cancer. Despite the apparent critical role in cancer, the molecular function and mode of action of LIN28 is not yet elucidated. To further understand the function of LIN28, we explored LIN28 mRNA targets in breast cancer cells using RNA-protein immunoprecipitation (RIP-Chip) followed by RNA sequencing. Using RIP-Chip and RNA sequencing we have identified a number of novel LIN28 targets in MCF-7 breast cancer cells. Therapeutic drugs inhibiting LIN28 could be promising in treatment of cancer. Our experiments also demonstrate that MG132, a proteasome inhibitor, inhibits LIN28 expression and modulates expression of LIN28 mRNA targets in breast cancer cells. The mechanism by which LIN28 regulates its targets is unknown; however, a number of the new targets are important in cancer. Previous studies suggest that LIN28 acts through translational mechanisms. Studies are ongoing to reveal the mechanisms by which LIN28 regulates bound targets and how proteasome inhibitors impact this regulation. 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 3082. doi:10.1158/1538-7445.AM2011-3082