Tumor‐associated macrophages promote prostate cancer progression via exosome‐mediated miR‐95 transfer

• Published in: Journal of cellular physiology 2020-12, Vol.235 (12), p.9729-9742
• Main Authors: Guan, Han, Peng, Rui, Fang, Fang, Mao, Likai, Chen, Zhijun, Yang, Shuai, Dai, Changyuan, Wu, Hongliang, Wang, Chengyong, Feng, Ninghan, Xu, Bin, Chen, Ming
• Format: Article
• Language: English
• Subjects: Cell fate; Cell interactions; Cell Line, Tumor; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Disease Progression; Epithelial-Mesenchymal Transition - genetics; Exosomes; Exosomes - genetics; Extracellular vesicles; Gene Expression Regulation, Neoplastic - genetics; Gene sequencing; Humans; JunB; JunB protein; Macrophages; Male; Mesenchyme; MicroRNAs - genetics; miR‐95; Molecular modelling; Neoplasms - genetics; Neoplasms - pathology; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Ribonucleic acid; RNA; Transcription Factors - genetics; Tumor cells; Tumor Microenvironment - genetics; Tumor-Associated Macrophages - metabolism; Tumor-Associated Macrophages - pathology; Tumors; tumor‐associated macrophages; Vesicles
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.29784

Tumor‐associated macrophages (TAMs) are vital constituents in mediating cell‐to‐cell communication within the tumor microenvironment. However, the molecular mechanisms underlying the interplay between TAMs and tumor cells that guide cell fate are largely undetermined. Extracellular vesicles, also known as exosomes, which are derived from TAMs, are the components exerting regulatory effects. Thus, understanding the underlying mechanism of “onco‐vesicles” is of crucial importance for prostate cancer (PCa) therapy. In this study, we analyzed micro RNA sequences in exosomes released by THP‐1 and M2 macrophages and found a significant increase in miR‐95 levels in TAM‐derived exosomes, demonstrating the direct uptake of miR‐95 by recipient PCa cells. In vitro and in vivo loss‐of‐function assays suggested that miR‐95 could function as a tumor promoter by directly binding to its downstream target gene, JunB, to promote PCa cell proliferation, invasion, and epithelial–mesenchymal transition. The clinical data analyses further revealed that higher miR‐95 expression results in worse clinicopathological features. Collectively, our results demonstrated that TAM‐mediated PCa progression is partially attributed to the aberrant expression of miR‐95 in TAM‐derived exosomes, and the miR‐95/JunB axis provides the groundwork for research on TAMs to further develop more‐personalized therapeutic approaches for patients with PCa. Our results demonstrated that TAM‐mediated prostate cancer (PCa) progression is partially attributed to the aberrant expression of miR‐95 in TAM‐derived exosomes, and the miR‐95/JunB axis provides the groundwork for research on tumor‐associated macrophages (TAMs) to further develop more‐personalized therapeutic approaches for patients with PCa.