Abstract 187: miR-1205/FRYL as a novel regulatory mechanism in androgen-independent prostate cancer
Authors: Durojaiye Victoria , Ilboudo Adeodat , Levine Fayola , Osborne Joseph , Park Jong Y. , Ogunwobi Olorunseun O. 
Published: August 2015

Prostate Cancer (PCa) is the second most common cause of cancer-related deaths in American men, mostly related to the development of androgen-independent PCa (AIPC). Understanding of the molecular mechanisms underlying the development of AIPC is critical to discovering more effective therapeutic strategies for AIPC. MicroRNAs (miRNAs) are short non-coding RNAs that play an important role in post-transcriptional regulation and have been implicated in cancer development. A recently annotated miRNA is miR-1205 encoded by the long non-coding PVT1 gene locus which is located at the prostate cancer susceptibility chromosomal region, 8q24. The role of miR-1205 in PCa is, however, unknown. This study aimed to determine whether miR-1205 plays an essential role in PCa progression. A panel of five prostate cell lines with a diversity of PCa characteristics was used. RWPE1, a non-tumorigenic prostate epithelial cell line, WPE1-NA22, an indolent PCa cell line derived from RWPE1 and three aggressive PCa cell lines (PC3, VCaP and MDA PCa 2b) were used. Expression of miR-1205 was determined using real-time quantitative polymerase chain reaction. We evaluated the effect of the loss or gain of miR-1205 by transfecting the oligonucleotide inhibitor or oligonucleotide mimic respectively. Effect of loss or gain of miR-1205 on proliferation and migration was measured using MTT and wound healing assays, respectively. The miSVR computer algorithm was used to ascertain putative targets. Effect of transfection of oligonucleotide mimic on mRNA expression of the putative targets was used to confirm the miR-1205 target. Our study indicates that the expression of miR-1205 is markedly less in PCa cells (WPE1-NA22, MDA PCa 2b, PC3, and VCaP) in comparison to the RWPE1 non-tumorigenic prostate epithelial cell line. The expression of miR-1205 was further significantly less in AIPC cells (PC3) compared to the other PCa cells. Loss of miR-1205 significantly increased cell proliferation in prostate epithelial cells. Exogenous miR-1205 significantly decreased cell proliferation in prostate epithelial cells. Also, loss of miR-1205 promoted migration in PCa cells by nearly 3 folds. The miSVR computer algorithm identified FRY-like (FRYL) as a putative target of miR-1205. Transfecting the oligonucleotide mimic of miR-1205 into androgen-independent PC3 cells leads to significant decrease in the expression of FRYL, suggesting that FRYL is a direct target of miR-1205. Therefore, miR-1205 regulates proliferation and migration of prostate epithelial cells, and loss of miR-1205 promotes a tumorigenic phenotype in PCa. Moreover, miR-1205 targets FRYL in AIPC. Consequently, strategies to increase miR-1205 or target FRYL may have therapeutic potential in AIPC.

Citation Format: Victoria Durojaiye, Adeodat Ilboudo, Fayola Levine, Joseph Osborne, Jong Y. Park, Olorunseun O. Ogunwobi. miR-1205/FRYL as a novel regulatory mechanism in androgen-independent 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 187. doi:10.1158/1538-7445.AM2015-187