The clinicopathological implication and prospective molecular mechanisms of miRNA-145-5p in the metastasis of prostate cancer (PCa) stand unclear. Herein, it is found that miRNA-145-5p expression was remarkably reduced in 131 cases of metastatic PCa than 1371 cases of localised ones, as the standardised mean differences (SMD) was -1.26 and the area under the curve (AUC) was 0.86, based on miRNA-chip and miRNA-sequencing datasets. The potential targets of miRNA-145-5p in metastatic PCa (n = 414) was achieved from the intersection of miRNA-145-5p transfected metastatic PCa cell line data, differential expression of metastatic PCa upregulated genes and online prediction databases. TOP2A was screened as one of the target hub genes by PPI network analysis, which was adversely related to miRNA-145-5p expression in both metastatic PCa (r = -0.504) and primary PCa (r = -0.281). Gene-chip and RNA-sequencing datasets, as well as IHC performed on clinical PCa samples, showed consistent upregulated expression of TOP2A mRNA and protein in PCa compared with non-PCa. The expression of TOP2A mRNA was also significantly higher in metastatic than localised PCa with the SMD being 1.72 and the AUC of sROC being 0.91. In summary, miRNA-145-5p may participate in PCa metastasis by binding TOP2A and be useful as a biomarker for the detection of metastatic PCa.

中文翻译：

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miRNA-145-5p 在前列腺癌转移中的表达和前瞻性分子机制。

miRNA-145-5p 在前列腺癌 (PCa) 转移中的临床病理学意义和前瞻性分子机制尚不清楚。在此，发现 miRNA-145-5p 在 131 例转移性 PCa 中的表达明显低于 1371 例局部转移性 PCa，标准化均数差 (SMD) 为 -1.26，曲线下面积 (AUC) 为 0.86 ，基于 miRNA 芯片和 miRNA 测序数据集。miRNA-145-5p 在转移性 PCa (n = 414) 中的潜在靶点是通过 miRNA-145-5p 转染的转移性 PCa 细胞系数据、转移性 PCa 上调基因的差异表达和在线预测数据库的交叉实现的。PPI网络分析将TOP2A筛选为靶基因之一，与转移性PCa中miRNA-145-5p的表达呈负相关（r = -0. 504) 和初级 PCa (r = -0.281)。与非 PCa 相比，基因芯片和 RNA 测序数据集以及对临床 PCa 样本进行的 IHC 显示 PCa 中 TOP2A mRNA 和蛋白质的表达一致上调。TOP2A mRNA 在转移灶中的表达也显着高于局部前列腺癌，SMD 为 1.72，sROC 的 AUC 为 0.91。总之，miRNA-145-5p可能通过结合TOP2A参与PCa转移，可用作检测转移性PCa的生物标志物。72 和 sROC 的 AUC 为 0.91。总之，miRNA-145-5p可能通过结合TOP2A参与PCa转移，可用作检测转移性PCa的生物标志物。72 和 sROC 的 AUC 为 0.91。总之，miRNA-145-5p可能通过结合TOP2A参与PCa转移，可用作检测转移性PCa的生物标志物。