Abstract 2284: MIR-200 family as EMT related microRNA in renal cell carcinoma

Abstract

Abstract (Background) Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney, and clear cell RCC represents the most common renal cancer histology. However surgical treatment is provided for localized disease, relapse or metastasis of the patient is caused in a considerable ratio. At present, metastatic RCC is difficult to treat and the process of metastasis is not well understood. Therefore, it is crucial to find molecular mechanisms based on recent genome analysis in RCC oncogenesis and metastasis. Based on the microRNA (miRNA) expression signature of RCC revealed that miR-200 family significantly reduced in RCC cells. The miR-200 family (miR-200b, miR-200a and miR-429 are encoded by single polycistronic transcript on chromosome 1p36.33 and miR-200c and miR-141 are cluster on chromosome 12 p13.31) of miRNA plays a major role to epithelial to mesenchymal transition (EMT) by targeting transcription repressors, zinc-finger E-box binding homeobox (ZEB1) and ZEB2. In this study, we investigated the functional significance of miR-200 family and identified the novel cancer pathways in RCC. (Methods) Cell proliferation and invasion assay was performed by restoration of mature miR-200 family (miR-200a, miR-200b, miR-200c, miR-429 and miR-141) in RCC cell lines. Genome-wide gene expression analysis was performed to identify the molecular networks of miR-200 family by microarray analysis. (Results) The mRNA expression levels of ZEB1 and ZEB2 were significantly decreased by miR-200 family (miR-200a, miR-200b, miR-200c, miR-429 and miR-141) transfectantion in RCC cells. Restoration of each miRNAs significantly inhibited cell proliferation and invasion in RCC cells. Interestingly, the morphological changes were recognized by miR-200 family transfection in RCC cell lines. Gene expression analysis showed more than ten candidate genes were searched for miR-200 family targets and these genes were up-regulated in RCC clinical specimens. (Conclusions) Our data suggest that miR-200 family function as tumor suppressors in RCC. EMT-related tumor suppressive miR-200 family mediates novel molecular targets provide new insights into the potential mechanisms of RCC oncogenesis and metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2284. doi:1538-7445.AM2012-2284