Abstract 2049: Post transcriptional regulation of RhoB expression

Abstract

Rho GTPases contribute to most steps of cancer initiation and progression, including the acquisition of unlimited proliferation potential, survival, tissue invasion and the establishment of metastases. By contrast to RhoA and RhoC, RhoB has been proposed to act as a tumor suppressor as it is activated in response to various stresses including UV exposure, and since it has been reported to inhibit tumor growth, cell migration and invasion. Unlike RhoA and RhoC, RhoB is often down regulated in human tumour tissues including lung and head and neck cancer and its expression is inversely correlated with tumor aggressiveness. However, the epigenetic regulation of RhoB expression in cancer cells remains to be elucidated. Since several recent works demonstrate that post-transcriptional deregulation of gene expression is involved in carcinogenesis, we have investigated the post-transcriptional regulation of RhoB expression. The RhoB 3’ untranslated region is well conserved between species and has numerous putative binding sites for post-transcriptional regulators such as mRNA binding proteins and microRNAs. By using luciferase assays and polysome analysis, we have found that the translation of the RhoB mRNA is regulated upon UV exposure. One specific miRNA, miR-19b whose expression is regulated by UV, directly targets the RhoB mRNA to control RhoB expression and UV-induced apoptosis. Interestingly, other post-transcriptionnal regulators involved in RhoB expression, such as the mRNA binding proteins HuR and TiaR were also indentified by functional assays using RNA interference strategy. Immunohistochemical analysis on a cohort of human lung tissues ranging from normal to invasive carcinoma are underway to detect a possible correlation between the expression of these proteins and RhoB downregulation in tumor. 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 2049.