BACKGROUND Human bone marrow mesenchymal stem cells (hBMSCs) are implicated in cancer initiation and metastasis, sometimes by releasing exosomes that mediate cell communication by delivering microRNAs (miRNAs). This study aimed to investigate the physiological mechanisms by which exosomal miR-205 derived from hBMSCs may modulate the growth of prostate cancer cells. METHODS Microarray-based gene expression profiling of prostate cancer was adopted to identify differentially expressed genes and regulatory miRNAs, which identified the candidates RHPN2 and miR-205 as the study focus. Then the binding affinity between miR-205 and RHPN2 was identified using in silico analysis and luciferase activity detection. Prostate cancer cells were co-cultured with exosomes derived from hBMSCs treated with either miR-205 mimic or miR-205 inhibitor. Subsequently, prostate cancer cell proliferation, invasion, migration, and apoptosis were detected in vitro. The effects of hBMSCs-miR-205 on tumor growth were investigated in vivo. RESULTS miR-205 was downregulated, while RHPN2 was upregulated in prostate cancer cells. RHPN2 was a target of miR-205, and upregulated miR-205 inhibited prostate cancer cell proliferation, invasion, and migration and promoted apoptosis by targeting RHPN2. Next, experiments demonstrated that hBMSCs-derived exosomes carrying miR-205 contributed to repressed prostate cancer cell proliferation, invasion, and migration and enhanced apoptosis. Furthermore, in vivo assays confirmed the inhibitory effects of hBMSCs-derived exosomal miR-205 on prostate cancer. CONCLUSION The hBMSCs-derived exosomal miR-205 retards prostate cancer progression by inhibiting RHPN2, suggesting that miR-205 may present a predictor and potential therapeutic target for prostate cancer.

中文翻译：

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人骨髓间充质干细胞衍生的含有 microRNA-205 的外泌体通过抑制 RHPN2 阻碍前列腺癌的进展。

背景人骨髓间充质干细胞（hBMSCs）与癌症的发生和转移有关，有时通过释放外泌体来传递微小RNA（miRNA）来介导细胞通讯。本研究旨在探讨源自 hBMSCs 的外泌体 miR-205 可能调节前列腺癌细胞生长的生理机制。方法采用基于微阵列的前列腺癌基因表达谱鉴定差异表达基因和调控miRNA，确定候选物RHPN2和miR-205为研究重点。然后使用计算机分析和荧光素酶活性检测鉴定 miR-205 和 RHPN2 之间的结合亲和力。前列腺癌细胞与来源于用 miR-205 模拟物或 miR-205 抑制剂处理的 hBMSCs 的外泌体共培养。随后，体外检测前列腺癌细胞增殖、侵袭、迁移和凋亡。在体内研究了 hBMSCs-miR-205 对肿瘤生长的影响。结果 miR-205 下调，而 RHPN2 在前列腺癌细胞中上调。RHPN2是miR-205的靶点，上调的miR-205通过靶向RHPN2抑制前列腺癌细胞增殖、侵袭和迁移并促进细胞凋亡。接下来，实验表明携带 miR-205 的 hBMSCs 衍生的外泌体有助于抑制前列腺癌细胞的增殖、侵袭和迁移并增强细胞凋亡。此外，体内试验证实了 hBMSCs 衍生的外泌体 miR-205 对前列腺癌的抑制作用。结论 hBMSCs 来源的外泌体 miR-205 通过抑制 RHPN2 延缓前列腺癌的进展，