Abstract 5219: MicroRNA-874 impedes angiogenesis in non-small cell lung cancer

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA MicroRNAs (miRs) are short (20-24nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in eukaryotes by affecting both the stability and translation of mRNAs. MicroRNAs play crucial roles in normal biological processes and are commonly dysregulated in human diseases. Thus far, miRs have been shown to act as either tumor suppressor genes or oncogenes in driving critical gene expression pathways in cancer stem cells in a wide range of human malignancies, including non-small cell lung cancer (NSCLC).We previously found that miR-874 could suppress tumor growth and metastasis of NSCLC. Since angiogenesis is important for tumor growth and metastasis, in this study, we further investigated the possible roles of miR-874 in tumor angiogenesis. Attenuation of miR-874 expression in histological sections of NSCLC tumors and the CD133 positive population of NSCLC cells (NSCLC-initiating cells; NSCLC-ICs), as compared to its normal counterparts, was observed by in situ hybridization and real time quantitative PCR, respectively. Tumor-conditioned medium from NSCLC-ICs induced significantly high levels of endothelial cell capillary network and neovascularization in vivo; whereas, re-expression of miR-874 in NSCLC-ICs inhibited this capillary network formation ability by suppressing the protein levels of VEGF, Stat3, MMP-2, uPA and PI3K. Further, miR-874-treatment decreased in vivo angiogenesis and pre-established orthotopic tumor growth in nude mice as compared to mock- and control-miR-treatments. Immunohistochemical analysis revealed a significant decrease in the expression of VEGF, Stat3 and microvessel density (CD31 levels) in xenograft tumor sections from miR-874-treated mice. In conclusion, our study highlights the possible anti-angiogenic role of miR-874 in NSCLC-initiating cells and presents a new, hopeful therapeutic target and prognostic marker for NSCLC. Citation Format: Chandramu Chetty, Dilip R. Maddirela, Venkateswara R. Gogineni, Subramanyam Chittivelu, Jasti S. Rao, Bhagavatula Moorthy. MicroRNA-874 impedes angiogenesis in non-small cell lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5219. doi:10.1158/1538-7445.AM2014-5219