Abu-Shahba Nourhan, Hegazy Elsayed, Khan Faiz M, Elhefnawi Mahmoud
Department of Medical Molecular Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.
Stem Cell Research Group, Medical Research Center of Excellence, National Research Centre, Cairo, Egypt.
Cancer Inform. 2023 May 10;22:11769351231171743. doi: 10.1177/11769351231171743. eCollection 2023.
Abnormal miRNA expression has been evidenced to be directly linked to HCC initiation and progression. This study was designed to detect possible prognostic, diagnostic, and/or therapeutic miRNAs for HCC using computational analysis of miRNAs expression. Methods: miRNA expression datasets meta-analysis was performed using the YM500v2 server to compare miRNA expression in normal and cancerous liver tissues. The most significant differentially regulated miRNAs in our study undergone target gene analysis using the mirWalk tool to obtain their validated and predicted targets. The combinatorial target prediction tool; miRror Suite was used to obtain the commonly regulated target genes. Functional enrichment analysis was performed on the resulting targets using the DAVID tool. A network was constructed based on interactions among microRNAs, their targets, and transcription factors. Hub nodes and gatekeepers were identified using network topological analysis. Further, we performed patient data survival analysis based on low and high expression of identified hubs and gatekeeper nodes, patients were stratified into low and high survival probability groups. Results: Using the meta-analysis option in the YM500v2 server, 34 miRNAs were found to be significantly differentially regulated (-value ⩽ .05); 5 miRNAs were down-regulated while 29 were up-regulated. The validated and predicted target genes for each miRNA, as well as the combinatorially predicted targets, were obtained. DAVID enrichment analysis resulted in several important cellular functions that are directly related to the main cancer hallmarks. Among these functions are focal adhesion, cell cycle, PI3K-Akt signaling, insulin signaling, Ras and MAPK signaling pathways. Several hub genes and gatekeepers were found that could serve as potential drug targets for hepatocellular carcinoma. POU2F1 and PPARA showed a significant difference between low and high survival probabilities (-value ⩽ .05) in HCC patients. Our study sheds light on important biomarker miRNAs for hepatocellular carcinoma along with their target genes and their regulated functions.
异常的miRNA表达已被证明与肝癌的发生和发展直接相关。本研究旨在通过对miRNA表达进行计算分析，检测肝癌可能的预后、诊断和/或治疗性miRNA。方法：使用YM500v2服务器对miRNA表达数据集进行荟萃分析，以比较正常和癌性肝组织中的miRNA表达。在我们的研究中，对差异调节最显著的miRNA使用mirWalk工具进行靶基因分析，以获得其已验证和预测的靶标。使用组合靶标预测工具miRror Suite获得共同调节的靶基因。使用DAVID工具对所得靶标进行功能富集分析。基于microRNA、其靶标和转录因子之间的相互作用构建网络。使用网络拓扑分析识别枢纽节点和守门人。此外，我们根据已识别的枢纽节点和守门人节点的低表达和高表达进行患者数据生存分析，将患者分为低生存概率组和高生存概率组。结果：使用YM500v2服务器中的荟萃分析选项，发现34种miRNA存在显著差异调节（P值⩽0.05）；5种miRNA下调，29种上调。获得了每种miRNA的已验证和预测靶基因，以及组合预测的靶标。DAVID富集分析产生了几个与主要癌症特征直接相关的重要细胞功能。这些功能包括粘着斑、细胞周期、PI3K-Akt信号传导、胰岛素信号传导、Ras和MAPK信号通路。发现了几个枢纽基因和守门人，它们可作为肝细胞癌的潜在药物靶点。POU2F1和PPARA在肝癌患者的低生存概率和高生存概率之间显示出显著差异（P值⩽0.05）。我们的研究揭示了肝细胞癌重要的生物标志物miRNA及其靶基因和调节功能。
