Abstract 2365: Intracellular interaction of downstream molecular mediators of miR-1207-3p in prostate cancer cells

Abstract

Abstract Prostate cancer (PCa) is the second most common cancer diagnosed among men in the United States. Human chromosome 8q24 is the most important PCa susceptibility locus. This region contains the MYC oncogene, which is involved in early PCa initiation. Downstream to MYC is the PVT1 gene, which is often amplified in PCa. PVT1 is a non-protein coding gene that encodes six annotated microRNAs (miRNAs), including miR-1207-3p. Our laboratory has previously demonstrated miR1207-3p to be a significant modulator in PCa and revealed that miR-1207-3p is significantly underexpressed in PCa cells and histologically confirmed PCa tissues compared to normal prostatic cells and tissues. We have also shown that miR-1207-3p has tumor suppressive activity in vivo. Moreover, we discovered that miR-1207-3p directly targets fibronectin type III domain containing 1 (FNDC1), which was found to be overexpressed in PCa cells and there is a concomitant overexpression of (FN1)/androgen receptor (AR)/c-MYC. In an effort to better understand the role of FNDC1/FN1/AR/c-MYC in PCa progression we examined the interaction between FNDC1/FN1/AR/c-MYC and found direct physical interaction through coimmunoprecipitation. We also examined the spatial localization of the FNDC1/FN1/AR/c-MYC pathway by performing immunofluorescence staining in PCa cells. Single staining analysis revealed that FNDC1 and c-MYC localize to the nucleus and cytoplasm while AR localizes to the nucleus and FN1 localizes to the cytoplasm in PCa cells. However, in normal prostate epithelial cells FNDC1, AR and c-MYC localize to the nucleus whereas FN1 localize to the cytoplasm. These results suggest that the underexpression of miR1207-3p may be affecting the localization of FNDC1 to cytoplasm and thus promoting interaction between FNDC1/FN1/AR/c-MYC. Future studies include examining the effect of miR-1207 on the spatial organization and interactions of the FNDC1/FN1/AR/c-MYC pathway through immunofluorescence and co-immunoprecipitation assays. Thus, understanding this molecular interaction could reveal interesting insight into the biology of microRNA-1207-3p regulation in PCa. Citation Format: Priyanka Ghosh, Oloronseun Ogunwobi. Intracellular interaction of downstream molecular mediators of miR-1207-3p in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2365.