Abstract 3070: Suppression of tumor cell invasiveness and in vivo tumor growth by microRNA-874 in non-small cell lung cancer.

Abstract

Abstract MicroRNAs are a family of small non-coding RNAs that regulate expression of many genes involved in normal development as well as human disorders including cancer. Here, we show that miR-874 plays a tumor suppressor role in non-small cell lung cancer (NSCLC) in vitro and in vivo. Interestingly, in silico target prediction analysis revealed numerous pro-oncogenes associated with tumor initiation, angiogenesis, invasion and migration, including MMP-2, uPA, NFAT5, PAK3, PAK7, LIMD, PECAM1, VEGF-A, Stat3, CUX1 and FGF1 as the putative target genes of miR-874. Our preliminary in situ hybridization experiments demonstrated the diminution of miR-874 expression in lung cancer tissues as compared to its normal counterparts. Overexpression of miR-874 in CD133-positive NSCLC cancer stem cell (CSC) population led to a significant loss in CSC phenotype and enhanced sphere de-differentiation into epithelial-like morphology. Restoration of miR-874 expression drastically reduced the invasive ability of cells in comparison to mock and control-miR treated cells by suppressing the protein levels of MMP-2 and uPA. Further, miR-874 treatment decreased orthotopic tumor growth in nude mice as compared to mock and control-miR treatments. Further, in vivo orthotopic tumor experiments in nude mice revealed the significant decrease in the immunoreactivity of human anti-MMP-2 and anti-uPA in miR-874-treated tumor sections. In conclusion, our study highlights the possible tumor suppressor role of miR-874 in NSCLC-initiating cells and suggests miR-874 as a potential target in the future treatment of NSCLC. Citation Format: Divya Kesanakurti, Dilip Maddirela, Subramanyam Chittivelu, Jasti S. Rao, Chandramu Chetty. Suppression of tumor cell invasiveness and in vivo tumor growth by microRNA-874 in non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3070. doi:10.1158/1538-7445.AM2013-3070 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.