Abstract 1462: Exosome-derived miR-429 contributes to prostate cancer chemoresistance

Abstract

Abstract Prostate cancer (PCa) is the most common cancer in men and the 2nd leading cause of cancer-related death in the United States. Certain miRNAs, act as tumor promoting or inhibiting factors in tumor development, function primarily by targeting specific mRNAs for degradation or inhibition of translation of their targeted proteins. Emerging evidence indicates that exosomes play a key role in tumor-host crosstalk, and exosome secretion, composition, and functional capacity are altered as tumors progress to aggressive phenotypes. From our prior report, we have constructed a potential network of 29 deregulated miRNAs, including 19 up and 10 down, in exosome samples derived from two kinds of paclitaxel resistant PCa cells (PC3-TXR and DU145-TXR) compared with their parental cells (PC3 and DU145). In this study, to further determine the roles of certain miRNAs derived from exosomes in chemoresistant cells, we firstly confirmed the lower expression level of miR-429 miRNA in the exosomes derived from the paclitaxel resistant PCa cells compared to their parental cells. In addition, when the miR-429 was over-expressed in PC3-TXR and DU145-TXR cells by stable transfection, epithelial-to-mesenchymal transition (EMT) markers significantly altered together with morphological changes. Overexpression of miR-429 decreased the tumor cell migration and invasion that associated with inactivation of PI-3K/AKT and Notch signaling pathways since the pathway specific inhibitors significantly diminished the transfected tumor cell migration and invasion. Finally, we found that overexpression of miRNA-429 significantly enhanced chemo-sensitivity of the chemoresistant PCa cells. These data suggested that exosome-derived miR-429 contributes to PCa chemoresistance and miR-429 may become a potential therapeutic target for PCa patients. This work was supported by Natural Science Foundation of China (NSFC) Key Project (81130046); NSFC (81171993; 81272415); Guangxi Projects of China (2013GXNSFEA053004; 2012GXNSFCB053004; 2013GXNSFBA019177; 1355004-5; 201201ZD004; GZPT13-35; 14122008-22; 11-031-05-K2; KY2015YB057; 14-045-12-K2). Note: This abstract was not presented at the meeting. Citation Format: Yang Liu, Liye Xie, Jing Li, Atsushi Mizokami, Evan T. Keller, Yi Lu, Jian Zhang. Exosome-derived miR-429 contributes to prostate cancer chemoresistance [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 1462. doi:10.1158/1538-7445.AM2017-1462