Abstract 175: miR-1207-3p-induced downregulation of fibronectin is a novel regulatory pathway in prostate cancer

Prostate cancer (PC) is the most commonly diagnosed male cancer in the western world. The molecular mechanisms underlying its development and progression are still unclear. Recent studies have established an important role for micro RNAs (miRNAs) in human cancers. miRNAs play a crucial role in post-transcriptional gene regulation. Some miRNAs have been implicated in PC. MicroRNA-1207-3p (miR-1207-3p) is encoded at the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PC susceptibility locus. This study aims to determine the role of miR-1207-3p in PC. miR-1207-3p expression was investigated in a panel of five PC cell lines representative of different characteristics of PC: WEP1-NA22 (derived from RWPE1, indolent, androgen dependent, White male), VCaP (aggressive, androgen-dependent, White male), MDA PCa 2b (aggressive, androgen-dependent, Black male), and PC-3 (aggressive, androgen-independent, White male), and compared to a non-tumorigenic prostate epithelial cell line, RWPE1 (White male). To evaluate the role of miR-1207-3p, effects of gain of expression and loss of expression on cell proliferation, migration and apoptosis were performed using an oligonucleotide mimic, an oligonucleotide inhibitor or a non-targeting negative control oligonucleotide. A target prediction algorithm was used to identify a putative target of miR-1207-3p, and confirmation of the target was done by assessing the effect of miR-1207-3p mimic on putative target expression using real-time PCR (qPCR) and western blotting. miR-1207-3p is significantly underexpressed (by almost 2-fold) in both indolent (WPE1-NA22) and aggressive (MDA PCa 2b, PC-3 and VCaP) human PC cell lines in comparison to normal prostate epithelial cells (RWPE1). This indicates that loss of miR-1207-3p may be an early event in PC development. Increased expression of miR-1207-3p in PC cells significantly inhibits proliferation, induces apoptosis and inhibits migration. Inhibition of miR-1207-3p expression in prostate epithelial cells causes a significant increase in proliferation, and a significant inhibition of apoptosis. Inhibition of miR-1207-3p expression led to a 4-fold increase in the migratory capacity of prostate epithelial cells. The miSVR computer algorithm identified fibronectin as a putative molecular target of miR-1207-3p. Forced expression of miR-1207-3p in prostate epithelial cells significantly reduced fibronectin expression. Fibronectin is significantly overexpressed in the PC cell lines in comparison to the non-tumorigenic prostate epithelial cell line. miR-1207-3p may have tumor suppressive effects in PC. These effects may be via direct targeting of fibronectin. In conclusion, we uncovered a miR-1207-3p-induced downregulation of fibronectin as a possible novel regulatory pathway in PC. Therefore, strategies to increase miR-1207-3p expression in PC cells may have therapeutic efficacy in PC. Citation Format: Dibash K. Das, Adeodat Ilboudo, Joseph R. Osborne, Olorunseun O. Ogunwobi. miR-1207-3p-induced downregulation of fibronectin is a novel regulatory pathway in prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 175. doi:10.1158/1538-7445.AM2015-175