Bioinformatics Analyses of Potential miRNA-mRNA Regulatory Axis in HBV-related Hepatocellular Carcinoma.
Bioinformatics Analyses of Potential miRNA-mRNA Regulatory Axis in HBV-related Hepatocellular Carcinoma.
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DOI：
10.7150/ijms.50126
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发表时间：
2021
影响因子：
3.6
通讯作者：
Tong GD
中科院分区：
文献类型：
--
作者：
Huang DP;Zeng YH;Yuan WQ;Huang XF;Chen SQ;Wang MY;Qiu YJ;Tong GD
目的：本研究旨在通过生物信息学分析探讨HBV相关性肝癌的miRNA-mRNA轴，为HBV相关性肝癌的病理生理机制和新的治疗方法的研究提供依据。研究方法：利用R软件对miRNA（GSE 76903）和mRNA（GSE 77509）数据集进行筛选，筛选差异表达的miRNA（DE-miRNA）和差异表达的mRNA（DE-mRNA）。DE-mRNAs和DE-miRNAs靶基因之间的重叠基因被鉴定为候选基因。通过cytohubba分析获得Hub基因。基于癌症基因组图谱（TCGA）数据，评估了中枢基因在蛋白质和mRNA水平的表达及其预后价值。根据预测的miRNA-mRNA对构建关键miRNA-mRNA轴。分别采用starBase v3.0和Kaplan-Meier Kaplan-Meier方法分析miRNA表达和预后作用。进行实时PCR以验证关键miRNA和mRNA的表达。使用starBase v3.0分析关键miRNA和mRNA的共表达。结果：筛选出CDK 1、CCNB 1、CKS 2和CCNE 1为枢纽基因，在蛋白质和mRNA水平上均显著上调。这些上调的枢纽基因也与不良预后显著相关。Hsa-mir-195- 5 p/CDK 1、hsa-mir-5589- 3 p/CCNB 1和hsa-let-7 c-3 p/CKS 2被筛选为关键miRNA-mRNA轴。HCC中的关键miRNAs减少，这表明预后不良。QPCR结果显示，HBV相关HCC中关键miRNAs减少，而关键mRNAs增加。进一步验证了在关键轴中miRNA与mRNA的反向关系。结论：本研究在HBV相关性HCC中发现了多个miRNA-mRNA轴。Hsa-mir-195- 5 p/CDK 1、hsa-mir-5589- 3 p/CCNB 1和hsa-let-7 c-3 p/CKS 2可作为HBV相关HCC的潜在预后标志物和治疗靶点。
Aims: We aimed to explore the crucial miRNA-mRNA axis through bioinformatics analysis and provide evidences for the development of pathophysiological mechanisms and new therapies for HBV-related HCC. Methods: MiRNA (GSE76903) and mRNA (GSE77509) dataset were used to screen differentially expressed miRNAs (DE-miRNAs) and differentially expressed mRNAs (DE-mRNAs) using R software. Overlapping genes between DE-mRNAs and target genes of DE-miRNAs were identified as candidate genes. Hub genes were obtained via cytohubba analysis. The expression at protein and mRNA levels and prognostic value of hub genes were evaluated based on The Cancer Genome Atlas (TCGA) data. Key miRNA-mRNA axes were constructed according to predicted miRNA-mRNA pairs. MiRNA expression and prognostic role were respectively identified using starBase v3.0 and Kaplan-Meier plotter database. Real-time PCR was performed to verify the expression of crucial miRNAs and mRNAs. Coexpression of crucial miRNA and mRNA were analyzed using starBase v3.0. Results: CDK1, CCNB1, CKS2 and CCNE1 were screened as hub genes, which were significantly upregulated at protein and mRNA levels. These up-regulated hub genes were also significantly associated with poor prognosis. Hsa-mir-195-5p/CDK1, hsa-mir-5589-3p/CCNB1 and hsa-let-7c-3p/CKS2 were screened as critical miRNA-mRNA axes. Critical miRNAs were decreased in HCC, which indicates unfavourable prognosis. QPCR results showed that crucial miRNAs were decreased, whereas critical mRNAs were increased in HBV-related HCC. A reverse relationship between miRNA and mRNA in crucial axis was further verified. Conclusion: This study identified several miRNA-mRNA axes in HBV-related HCC. Hsa-mir-195-5p/CDK1, hsa-mir-5589-3p/CCNB1 and hsa-let-7c-3p/CKS2 might serve as potential prognostic biomarkers and therapeutic targets for HBV-related HCC.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
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影响因子：
14.9
作者：
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通讯作者：
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影响因子：
0.7
作者：
Ge, Wei;Yu, De-Cai;Ding, Yi-Tao
通讯作者：
Ding, Yi-Tao
鉴定有助于 HBV 相关 HCC 发病机制的潜在 miRNA-mRNA 调控网络
影响因子：
7.4
作者：
Lou, Weiyang;Liu, Jingxing;Fan, Weimin
通讯作者：
Fan, Weimin
影响因子：
3.6
作者：
Fang, Yifeng;Yu, Hong;Cai, Xiujun
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Cai, Xiujun