Prostate cancer (PCa) is the most common non-skin cancer and the second leading cause of cancer-related death for men in the U.S. A major challenge is understanding the molecular mechanisms involved in the progression from the asymptomatic androgen-dependent PCa to the lethal castration resistant prostate cancer (CRPC). The chromosomal region 8q24 is associated with aggressive PCa and variants of this region have been identified to interact with the PVT1 non-coding gene in PCa. In previous work we demonstrated that microRNA-1207-3p (miR-1207-3p) has prognostic value in PCa, and directly binds to the 3’ UTR of Fibronectin type III domain containing 1 (FNDC1) to regulate a novel FNDC1/fibronectin (FN1)/androgen receptor (AR) pathway upregulated in metastatic PCa. miR-1207-3p is encoded at the PVT1 gene locus, which is located downstream of c-Myc on the 8q24 human chromosomal region. Studies have suggested amplification at the 8q24 human chromosomal region, which includes C-Myc, as a possible prognostic factor for CRPC. c-Myc is a well-established proto-oncogene that is commonly found to be amplified in up to 72% of CRPCs significant amplication of c-myc has been a consequence of antiandrogen treatment, and c-Myc is downstream of AR in some PCa. miRNAs have also been implicated in the regulation of c-Myc. Nevertheless, the mechanisms regulating c-Myc remain unclear in PCa. Using a panel of five PCa cell lines we discovered that c-Myc expression is higher in aggressive CRPC cell lines compared to non-aggressive CRPC and androgen-dependent prostate cancer cell lines. Furthermore, our data reveals that c-Myc expression is higher in the aggressive E006AA-hT PCa cell line when compared to the indolent E006AA PCa cell line. This suggests that c-Myc is associated with aggressive PCa. Moreover, overexpression of miR-1207-3p suppresses the expression of c-Myc in E006AA-hT PCa cells but not E006AA PCa cell line in which c-Myc is underexpressed compared to the normal prostate epithelial cell line, RWPE-1. Next, using a synthetic biotinylated miR-1207-3p duplex, we discovered that overexpression of miR-1207-3p more effictively inhibited migration, inhibited proliferation and increased apoptosis in the aggressive E006AA-hT PCa cell line with increased c-Myc expression when compared to the indolent E006AA PCa cell line with decreased c-Myc expression. These data demonstrate that the miR-1207-3p/FNDC1/FN1/AR pathway may regulate c-Myc in aggressive PCa.
Citation Format: Dibash K. Das, Olorunseun O. Ogunwobi. miR-1207-3p regulates c-Myc in aggressive prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1473. doi:10.1158/1538-7445.AM2017-1473