Abstract MIP-050: NON–CODING GENETIC ABERRATIONS IN HIGH GRADE SEROUS OVARIAN CANCER

Abstract

Abstract BACKGROUND The 3q26.2 loci amplification is present in a large proportion of high grade serous ovarian cancer (HGSOC) is less frequently curable disease in the clinic. The 3q26.2 loci, which is present in at least 35% of HGSOC, is large and structurally complex suggesting that multiple coding genes of the amplicon contribute to tumor initiation and progression either alone or through cooperative activity. Our high resolution SNP array mapping of 3q26.2 amplicon identified microRNAs miR569 and miR551b are highly amplified in addition to the coding genes in a large set of ovarian cancer samples. Potential role of miR569 and miR551b are not characterized previously in the context of ovarian cancer. Herein our studies provide new mechanisms underlying the oncogenic role of microRNAs amplified in 3q26 in ovarian cancer. RESULTS We demonstrated a strong correlation between 3q26.2 amplification and overexpression of miR569 in patient's samples of ovarian cancer. Using target based analysis, AGOCLIP methods, cellular and molecular approaches, we have demonstrated that 3q26 microRNAs altered the expression of TP53INP1, P53AIP1, and STAT3, which are critical regulators of survival and proliferation of ovarian cancer cells. Employing in silico and in vitro experiments, we have showed that miR569 directly targets and inhibited the expression of p53 induced tumor suppressor gene TP53INP1. miRNAs are thought to primarily downregulate the gene expression by binding 3'UTR of target genes. Our recent results identified a novel action of microRNAs, that miR551b can bind to the promoter of STAT3 and activate STAT3 transcription by recruiting transcription factors and RNA–Polymerase–II to the promoter. In sum, the discovery of miRNAs and lncRNAs as potent regulators of RNA stability and translation, dramatically changed our understanding of the mechanisms controlling the gene expression and protein levels. We are expecting that our studies will identify new biomarkers and novel targets for therapy. Citation Format: Pradeep Chaluvally–Raghavan, PhD. NON–CODING GENETIC ABERRATIONS IN HIGH GRADE SEROUS OVARIAN CANCER [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr MIP-050.