Department of Human Genetics, Sri Ramachandra Institute of Higher Education and Research, Chennai, 600116, India.
Central Research Facility, Sri Ramachandra Institute of Higher Education and Research, Chennai, India.
Mol Biol Rep. 2021 Apr;48(4):3349-3356. doi: 10.1007/s11033-021-06384-z. Epub 2021 May 4.
Prostate cancer is the leading cause of death among men worldwide. Deregulation of microRNAs has been reported in many cancers. Expression of microRNAs miR-20a-5p, miR-21-5p, miR-100-5p, miR-125a-5p and miR-146a-5p in tissue blocks of histologically confirmed prostate cancer patients compared with BPH patients, to identify potential microRNA biomarker for prostate cancer. MicroRNA was isolated and expression was quantified by qRT-PCR using Taqman Advanced microRNA assay kits. The interactions between the microRNA:target mRNA were predicted by using bioinformatics tools such as miRwalk and miRTargetlink. The experimentally validated targets were analysed using gprofiler to identify their molecular function, biological process and related pathways. The expression analysis revealed that miR-21 and miR-100 were significantly down-regulated whereas miR-125a was up-regulated in prostate cancer patients. Comparative analysis of the expression levels with tumor grading reveal that miR-100 was significantly down-regulated (p < 0.05) in high grade tumor, indicating that miR-100 associated with prostate cancer. ROC analysis revealed that combined analysis of down-regulated miRNAs (miR-21 and miR-100) shown AUC of 0.72 (95% CI 0.65-0.79). The combined analysis of all five miRNAs showed AUC of 0.87 (95% CI 0.81-0.92). The targets prediction analysis revealed several validated targets including BCL2, ROCK1, EGFR, PTEN, MTOR, NAIF1 and VEGFA. Our results provide evidence that combined analysis of all the five miRNAs as a panel can significantly improve the prediction level of the presence of prostate cancer and may be used as a potential diagnostic biomarker.
前列腺癌是全球男性死亡的主要原因。已经有报道称，许多癌症中存在 microRNA 的失调。与 BPH 患者相比，在组织学证实的前列腺癌患者的组织块中比较 microRNAs miR-20a-5p、miR-21-5p、miR-100-5p、miR-125a-5p 和 miR-146a-5p 的表达，以确定前列腺癌的潜在 microRNA 生物标志物。使用 Taqman 高级 microRNA 检测试剂盒通过 qRT-PCR 分离 microRNA 并定量表达。使用 miRwalk 和 miRTargetlink 等生物信息学工具预测 microRNA:靶 mRNA 的相互作用。使用 gprofiler 分析实验验证的靶标，以确定其分子功能、生物学过程和相关途径。表达分析显示，miR-21 和 miR-100 在前列腺癌患者中显著下调，而 miR-125a 上调。与肿瘤分级的表达水平比较显示，miR-100 在高级别肿瘤中显著下调（p<0.05），表明 miR-100 与前列腺癌相关。ROC 分析显示，下调 microRNAs（miR-21 和 miR-100）的联合分析显示 AUC 为 0.72（95%CI 0.65-0.79）。所有五个 microRNAs 的联合分析显示 AUC 为 0.87（95%CI 0.81-0.92）。靶标预测分析显示了几个经过验证的靶标，包括 BCL2、ROCK1、EGFR、PTEN、MTOR、NAIF1 和 VEGFA。我们的研究结果表明，将所有五个 microRNAs 的联合分析作为一个面板，可以显著提高前列腺癌存在的预测水平，并可能作为一种潜在的诊断生物标志物。
