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

Abstract

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.

LncRNA nuclear‐enriched abundant transcript 1 shuttled by prostate cancer cells‐secreted exosomes initiates osteoblastic phenotypes in the bone metastatic microenvironment via miR‐205‐5p/runt‐related transcription factor 2/splicing factor proline‐ and glutamine‐rich/polypyrimidine tract‐binding protein 2 axis

“…Prostate cancer (PCa) constitutes the most prevalent cancer in men, accounting for the second major cause of deaths associated with cancer. 1 Moreover, PCa exhibits a strong tendency to metastasize to bones, such that up to 90% of patients with advanced PCa suffer from bone metastasis. 2 These bone metastases can precipitate a plethora of bone complications, which greatly influence the quality of life of patients.…”

Roles and mechanisms of exosomal non-coding RNAs in human health and diseases

“… 326 Tumor-associated macrophages enhances PCa progression through exosomal miR-95. 327 MiR-183 encapsulated in exosomes is upregulated in PCa patients and promotes proliferation, migration, and invasion of tumor cell by downregulating expression of TPM1. 328 Ye et al reported that exosomal miR-141-3p promotes osteoblastic metastasis of PCa by modulating activity of osteoblasts.…”

Extracellular vesicles in prostate cancer: a narrative review

“…Prostate cancer-derived EVs downregulate natural killer group 2, member D expression on natural killer and CD8+ T cells, thereby promoting immune evasion (180). Tumor-associated macrophages promote prostate cancer progression by EV-mediated transfer of miR-95 (181).…”