Abstract 1838: Differential CXCL13 and CXCR5 expression mediated by down-regulation of select miRNAs in prostate cancer

Abstract

Abstract Chemokines and their receptors are involved in the inflammatory response by attracting immune cells to sites of infection and wound healing. Chemokines have also been implicated in the progression of prostate cancer (PCa). We have previously shown a positive correlation between the expression of CXCL13 and CXCR5 proteins with PCa progression; in particular, the CXCR5 protein is expressed to a greater extent by prostate tumors isolated from African Americans than compared to those from European Americans. In the present study, we sought: (i) to determine whether CXCL13 and CXCR5 mRNA expression patterns correlated with overall and/or disease-free survival in PCa cases and (ii) to identify the possible molecular mechanisms that govern this association. CXCL13 and CXCR5 mRNA levels and PCa survival rates were evaluated using The Cancer Genome Atlas (TCGA) data sets and the CbioPortal, respectively. CXCR5 and CXCL13 mRNA expression did not correlate with prostate tumor stage or grade and was not associated with overall PCa survival. However, CXCR5 mRNA expression was significantly associated with poor disease-free survival. Gene map analysis using the UCSC Genome Browser revealed consensus sequence binding sites for four miRNA's (miR-192/215, miR-486, and miR-494) that could bind the 3’ UTR of the cxcr5 transcript. Our results showed that miR-494 was frequently deleted or down-regulated, confirming other reports that miR-494 is down-regulated in high-grade PCa cases. Of note, miR-494 also targets cxcr4 mRNA and suppresses migration of PCa cells. Others have shown that miR-486 is associated with p53 and PI3K-Akt pathways and miR-186 has a putative binding site in the 3’ UTR region of the cxcl13 transcript. This miRNA was down-regulated in PCa patients with initial metastasis. These results confirm our previous studies demonstrating a correlation between tumor expression and PCa progression and reveal new mechanisms of post-translational regulation of this chemokine receptor. Citation Format: Denise E. Hinton, James Lillard. Differential CXCL13 and CXCR5 expression mediated by down-regulation of select miRNAs in prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1838.