A number of studies have reported that aberrant expression of microRNAs (miRNAs) closely correlates with the bone metastasis of prostate cancer (PCa). However, clinical significance and functional roles of both strands of a single miRNA in bone metastasis of PCa remain undefined. Here, we reported that miR-582-3p and miR-582-5p expression were simultaneously reduced in bone metastatic PCa tissues compared with non-bone metastatic PCa tissues. Downexpression of miR-582-3p and miR-582-5p strongly and positively correlated with advanced clinicopathological characteristics and shorter bone metastasis-free survival in PCa patients. Upregulating miR-582-3p and miR-582-5p inhibited invasion and migration abilities of PCa cells , as well as repressed bone metastasis . Our results further revealed that miR-582-3p and miR-582-5p attenuated bone metastasis of PCa via inhibiting transforming growth factor β (TGF-β) signaling by simultaneously targeting several components of TGF-β signaling, including SMAD2, SMAD4, TGF-β receptor I (TGFBRI), and TGFBRII. Moreover, deletion contributes to miR-582-3p and miR-582-5p downexpression in PCa tissues. Finally, clinical negative correlations of miR-582-3p and miR-582-5p with SMAD2, SMAD4, TGFBRI, and TGFBRII were demonstrated in PCa tissues. Thus, our findings explore a novel tumor-suppressive miRNA with its both strands implicated in bone metastasis of PCa, suggesting its potential therapeutic value in treatment of PCa bone metastasis.

中文翻译：

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miR-582-3p 和 miR-582-5p 通过抑制 TGF-β 信号传导抑制前列腺癌骨转移


多项研究报道，microRNA（miRNA）的异常表达与前列腺癌（PCa）的骨转移密切相关。然而，单个 miRNA 的两条链在 PCa 骨转移中的临床意义和功能作用仍不清楚。在这里，我们报道与非骨转移性 PCa 组织相比，骨转移性 PCa 组织中 miR-582-3p 和 miR-582-5p 的表达同时降低。 miR-582-3p和miR-582-5p的下调与PCa患者的晚期临床病理特征和较短的无骨转移生存期呈强烈正相关。上调miR-582-3p和miR-582-5p可抑制PCa细胞的侵袭和迁移能力，并抑制骨转移。我们的结果进一步表明，miR-582-3p和miR-582-5p通过同时靶向TGF-β信号传导的多个成分（包括SMAD2、SMAD4、TGF）来抑制转化生长因子β（TGF-β）信号传导，从而减弱前列腺癌的骨转移-β 受体 I (TGFBRI) 和 TGFBRII。此外，缺失导致前列腺癌组织中 miR-582-3p 和 miR-582-5p 的表达下调。最后，在 PCa 组织中证明了 miR-582-3p 和 miR-582-5p 与 SMAD2、SMAD4、TGFBRI 和 TGFBRII 的临床负相关性。因此，我们的研究结果探索了一种新型肿瘤抑制 miRNA，其双链均与 PCa 骨转移有关，表明其在治疗 PCa 骨转移中具有潜在的治疗价值。