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.
Journal of cellular physiology. 2020 May 14 [Epub ahead of print]
Han Guan, Rui Peng, Fang Fang, Likai Mao, Zhijun Chen, Shuai Yang, Changyuan Dai, Hongliang Wu, Chengyong Wang, Ninghan Feng, Bin Xu, Ming Chen
Department of Urology, First Affiliated Hospital of Bengbu Medical College, Bengbu, China., Department of Immunology, School of Laboratory Medicine, Anhui Provincial Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu, China., Department of Urology, Second Affiliated Hospital of Bengbu Medical College, Bengbu, China., Department of Urology, Affiliated Wuxi No.2 Hospital of Nanjing Medical University, Wuxi, China., Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.