Abstract 965: Exosome-derived microRNAs contributes to prostate cancer chemoresistance

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Abstract Accumulating evidence has demonstrated that certain miRNAs play important roles in cancer cell chemoresistance. However, the pleotropic functions of exosome-derived miRNAs on developing chemoresistance remain unknown. In this study, we aimed to build potential networks of miRNAs, which derived from the exosome of chemoresistant prostate cancer (PCa) cells, with their known target genes using miRNA expression profiling and bioinformatic tools. Global miRNA expression profiles were measured by microarray. Twelve miRNAs were initially selected and validated by qRT-PCR. Known targets of deregulated miRNAs were utilized using DIANA-TarBase database v6.0. The incorporation of deregulated miRNAs and target genes into KEGG pathways were utilized using DIANA-mirPath software. To construct potential miRNA regulatory networks, the overlapping parts of two selected KEGG pathways were visualized by Cytoscape software. We identified 29 deregulated miRNAs, including 19 up and 10 down, in exosome samples derived from two kinds of paclitaxel resistance PCa cells (PC3-TXR and DU145-TXR) compared with their parental cells (PC3 and DU145). The enrichment results of deregulated miRNAs and known target genes showed that a few pathways were correlated with several critical cell signaling pathways. We found that hub hsa-16-5p, hsa-miR-3915, hsa-miR-488-3p, hsa-miR-5004-5p, hsa-miR-23c, hsa-miR-3673, hsa-miR-3654, and hsa-miR-32-5p were potential targets to hub androgen receptor (AR) and phosphatase and tensin homolog (PTEN). Hub TCF4 target genes were mainly regulated by hub hsa-miR3176, hsa-miR-141-3p, hsa-miR-606, hsa-miR381, and hsa-miR-429 miRNAs. These results may provide a linkage between PCa chemoresistance and exosome regulatory networks and thus lead us to propose that PTEN and TCF4 genes may be the important genes which regulated by exosome miRNAs in chemoresistance cancer cells. Supported by NSFC Key Project 81130046; NSFC Project 81171993 and NSFC81272415; Guangxi Key Projects 2013GXNSFEA053004 and 2012GXNSFCB053004; Guangxi Ministry of Education grants 201202ZD022 and 201201ZD004. Citation Format: JIng Li, Xiaozhen Xu, Hao Guan, Atsushi Mizokami, Evan T. Keller, Xin Yang, Xia Liu, Jiyong Tan, Longyuan Hu, Yi Lu, Jian Zhang. Exosome-derived microRNAs contributes to prostate cancer chemoresistance. [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 965.

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