miRNA 和 mRNA 整合网络构建揭示左侧和右侧结肠癌的新关键调控因子。
miRNA and mRNA Integration Network Construction Reveals Novel Key Regulators in Left-Sided and Right-Sided Colon Adenocarcinoma.
机构信息
Graduate School, Tianjin University of Traditional Chinese Medicine, China.
Department of Gastrointestinal Surgery, Nankai Clinical College of Tianjin Medical University, China.
出版信息
Biomed Res Int. 2019 Apr 3;2019:7149296. doi: 10.1155/2019/7149296. eCollection 2019.
BACKGROUND
The distinction between right-sided and left-sided colon adenocarcinoma has recently received considerable. This study aims to identify key MicroRNA (miRNA) and mRNAs in right-sided colon adenocarcinoma (RSCOAD) and left-sided colon adenocarcinoma (LSCOAD) by TCGA integration analysis.
METHODS
The miRNA and mRNA expression profiles of a large group of patients with RSCOAD and LSCOAD were obtained from TCGA. The differentially expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) were identified by TCGA integration analysis. The optimal diagnostic miRNA biomarkers for RSCOAD and LSCOAD were identified by Boruta algorithm. We established classification models to distinguish RSCOAD and LSCOAD. Protein-protein interaction (PPI) network analysis, DEmiRNA-DEmRNA interaction analysis, and functional annotation were performed. The expression of selected DEmiRNAs and DEmRNAs was validated by qRT-PCR.
RESULTS
A total of 2534 DEmRNAs (940 downregulated and 1594 upregulated mRNAs) and 54 DEmiRNAs (22 downregulated and 32 upregulated miRNAs) between RSCOAD and LSCOAD were identified. The feature selection procedure was to obtain 22 optimal diagnostic miRNAs biomarkers in RSCOAD compared to LSCOAD. The AUC of the random forests model was 0.869 and the specificity and sensitivity of this model were 79% and 84.6%, respectively. Three DEmiRNAs (hsa-miR-224-5p, hsa-miR-155-5p, and hsa-miR-31-5p) and five DEmRNAs (CXCR4, SMAD4, KRAS, FITM2, and PLAGL2) were identified key DEmiRNAs and DEmRNAs in RSCOAD compared to LSCOAD. The qRT-PCR results of CXCR4, FITM2, TFAP2A, ULBP2, hsa-miR-224-5p, and hsa-miR-155-5p were consistent with our integrated analysis.
CONCLUSION
A total of three DEmiRNAs (hsa-miR-224-5p, hsa-miR-155-5p, and hsa-miR-31-5p) and five DEmRNAs (CXCR4, SMAD4, KRAS, FITM2, and PLAGL2) may be involved in the pathogenesis of RSCOAD and LSCOAD which may make a contribution for understanding mechanisms and developing therapeutic strategies for RSCOAD and LSCOAD.
背景
右侧和左侧结肠癌之间的区别最近受到了相当大的关注。本研究旨在通过 TCGA 整合分析鉴定右侧结肠癌（RSCOAD）和左侧结肠癌（LSCOAD）中的关键 MicroRNA（miRNA）和 mRNA。
方法
从 TCGA 中获得了大量 RSCOAD 和 LSCOAD 患者的 miRNA 和 mRNA 表达谱。通过 TCGA 整合分析鉴定差异表达的 miRNA（DEmiRNA）和 mRNA（DEmRNA）。通过 Boruta 算法鉴定 RSCOAD 和 LSCOAD 的最佳诊断 miRNA 生物标志物。我们建立了分类模型来区分 RSCOAD 和 LSCOAD。进行蛋白质-蛋白质相互作用（PPI）网络分析、DEmiRNA-DEmRNA 相互作用分析和功能注释。通过 qRT-PCR 验证选定的 DEmiRNA 和 DEmRNA 的表达。
结果
在 RSCOAD 和 LSCOAD 之间共鉴定出 2534 个 DEmRNA（940 个下调和 1594 个上调 mRNAs）和 54 个 DEmiRNA（22 个下调和 32 个上调 miRNAs）。特征选择过程是在 RSCOAD 中获得 22 个最佳诊断 miRNA 生物标志物，与 LSCOAD 相比。随机森林模型的 AUC 为 0.869，该模型的特异性和敏感性分别为 79%和 84.6%。与 LSCOAD 相比，在 RSCOAD 中鉴定出 3 个 DEmiRNA（hsa-miR-224-5p、hsa-miR-155-5p 和 hsa-miR-31-5p）和 5 个 DEmRNA（CXCR4、SMAD4、KRAS、FITM2 和 PLAGL2）为 RSCOAD 中的关键 DEmiRNA 和 DEmRNA。CXCR4、FITM2、TFAP2A、ULBP2、hsa-miR-224-5p 和 hsa-miR-155-5p 的 qRT-PCR 结果与我们的整合分析一致。
结论
三个 DEmiRNA（hsa-miR-224-5p、hsa-miR-155-5p 和 hsa-miR-31-5p）和五个 DEmRNA（CXCR4、SMAD4、KRAS、FITM2 和 PLAGL2）可能参与了 RSCOAD 和 LSCOAD 的发病机制，这可能有助于我们理解 RSCOAD 和 LSCOAD 的发病机制，并为开发治疗策略做出贡献。
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