RNA Binding Proteins Posttranscriptionally Regulate Genes Involved In Oncogenesis

摘要

Whereas transcriptional gene regulation is well studied, posttranscriptional gene control is poorly understood. Yet, emerging evidence indicates that posttranscriptional control by RNA binding proteins (RBPs) and microRNAs (miRNAs) are important key regulators of gene expression of many cancer related genes. The RBP, HuR, is a master regulator of many early response genes in cancer. Of the six classical acquired traits first proposed by Hanahan and Weinberg that malignantly transformed cells develop, HuR has been demonstrated to control genes in multiple areas. The purpose of this research is to define the in vivo mRNA targets of the RNA binding protein, HuR using RNA immunoprecipitations applied to microarray chips (RIP-Chip) in estrogen positive (ER+) and estrogen negative (ER-) breast cancer. Additionally, we will test the hypothesis that HuR increases cell proliferation by regulating mRNAs involved in breast oncogenesis at the posttranscriptional level. We will do this by altering HuR levels in breast cancer cell lines using lentiviral short hairpin RNAi to knock down and also over-express HuR and assay tumor formation by injection into athymic nude mice (orthotopic model).