Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China.
Division of Spinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China.
IET Syst Biol. 2021 Feb;15(1):1-13. doi: 10.1049/syb2.12011. Epub 2021 Feb 1.
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.
miRNA-145-5p 在前列腺癌（PCa）转移中的临床病理意义和潜在分子机制尚不清楚。本文通过 miRNA 芯片和 miRNA 测序数据集发现，与 1371 例局部 PCa 相比，131 例转移性 PCa 中 miRNA-145-5p 的表达显著降低，标准化均数差（SMD）为-1.26，曲线下面积（AUC）为 0.86。转移性 PCa（n=414）中 miRNA-145-5p 的潜在靶基因是从 miRNA-145-5p 转染转移性 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集获得的。通过 PPI 网络分析筛选出 TOP2A 作为靶基因的一个枢纽基因，TOP2A 在转移性 PCa（r=-0.504）和原发性 PCa（r=-0.281）中与 miRNA-145-5p 的表达呈负相关。基因芯片和 RNA-seq 数据集以及对临床 PCa 样本进行的 IHC 显示，TOP2A mRNA 在 PCa 中的表达明显高于非 PCa。转移性 PCa 中 TOP2A mRNA 的表达也明显高于局部性 PCa，SMD 为 1.72，sROC 的 AUC 为 0.91。总之，miRNA-145-5p 可能通过与 TOP2A 结合参与 PCa 的转移，并且可以作为检测转移性 PCa 的生物标志物。
