Prostate carcinoma cell-derived exosomal MicroRNA-26a modulates the metastasis and tumor growth of prostate carcinoma

• Published in: Biomedicine & pharmacotherapy Vol. 117; p. 109109
• Main Authors: Wang, Xiaobin, Wang, Xi, Zhu, Zhiyi, Li, Wensheng, Yu, Guoqiang, Jia, Zhaohui, Wang, Xiangwei
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.09.2019
• Subjects: Animals; Castration-resistant prostate carcinoma; Cell Line, Tumor; Cell Movement; Cell Proliferation; Epithelial-Mesenchymal Transition - genetics; Exosomes; Exosomes - metabolism; Exosomes - ultrastructure; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; microRNA-26a; MicroRNAs - genetics; MicroRNAs - metabolism; Neoplasm Invasiveness; Neoplasm Metastasis; Prostate carcinoma; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Prostate carcinoma; microRNA-26a; Exosomes; Castration-resistant prostate carcinoma
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2019.109109

Prostate carcinoma may develop into metastatic castration-resistant prostate carcinoma (mCRPC) after endocrine therapy. Exosomal microRNAs play an important role in the regulation of tumor microenvironment. Our study aimed to investigate the effect of exosomal miR-26a on tumor phenotype of prostate carcinoma. Low-grade prostate carcinoma cell line (LNCAP) and mCRPC cell line (PC-3) were treated as experimental subjects according to their miR-26a expressions. Wound healing, transwell and colony-forming unit assays were performed after miR-26a mimic/inhibitor transfection. Then, exosomes were isolated from LNCAP and PC-3 cells, and the levels of exosomal miR-26a were determined. After co-culture of LNCAP (PC-3) cells with PC-3 (LNCAP) exosomes, changes in malignant behaviors were measured. Moreover, LNCAP/PC-3 exosomes were injected into xenograft tumor mice to determine effects of the exosomes on tumorigenicity of LNCAP and PC-3 cells. MiR-26a showed a potently inhibitory effect on cell proliferation, migration and invasion of LNCAP and PC-3 cells. LNCAP exosomes had a higher miR-26a level, compared with PC-3 exosomes. Overexpression of miR-26a attenuated the enhanced malignant behavior of LNCAP cells induced by PC-3 exosomes, and miR-26a inhibition could reverse the inhibitory effects of LNCAP exosomes on PC-3 cells. Exosomal miR-26a could significantly alter the expressions of epithelial-mesenchymal transition (EMT)-related factors. Moreover, LNCAP exosomes suppressed the tumorigenicity of PC-3 cells, while PC-3 exosomes could promote the tumorigenicity of LNCAP cells. Our data suggest that exosomal miR-26a derived from prostate carcinoma cells had a suppressive effect on the metastasis and tumor growth of prostate carcinoma.