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预测可干扰胶质母细胞瘤中 和 的基因调控活性的长链非编码RNA。

LncRNAs Predicted to Interfere With the Gene Regulation Activity of and in GBM.

作者信息

Zheng Jingfang, Su Zhiying, Kong Yang, Lin Qingping, Liu Hongli, Wang Yanlong, Wang Jian

机构信息

Department of Gynecology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, China.

Department of Reproductive Medicine, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, China.

出版信息

Front Oncol. 2020 Mar 9;10:303. doi: 10.3389/fonc.2020.00303. eCollection 2020.

Abstract

Rigorous molecular characterization of biological systems has uncovered a variety of gene variations underlying normal and disease states and a remarkable complexity in the forms of RNA transcripts that exist. A recent concept, competitive endogenous RNA, suggests that some non-coding RNAs can bind to miRNAs to modulate their role in gene expression. Here, we used several platforms, integrating mRNA, non-coding RNAs and protein data to generate an RNA-protein network that may be dysregulated in human glioblastoma multiforme (GBM). Publicly available microarray data for mRNA and miRNA were used to identify differentially expressed miRNAs and mRNAs in GBM relative to non-neoplastic tissue samples. Target miRNAs were further selected based on their prognostic significance, and the intersection of their target gene set with the differentially expressed gene set in Venn diagrams. Two miRNAs, miR-637 and miR-196a-5p, were associated with poor and better prognosis, respectively, in GBM patients. Non-coding RNAs, ENSG00000203739/ENSG00000271646 and TPTEP1, were predicted to be miRNA target genes for miR-637 and miR-196a-5p and positively correlated with the selected mRNA, CYBRD1 and RUFY2. A local protein interaction network was constructed using these two mRNAs. Predictions based on the ENSG00000203739/ENSG00000271646-miR-637-CYBRD1 and TPTEP1-miR-196a-5p-RUFY2 regulation axes indicated that the two proteins may act as an oncogene and tumor suppressor, respectively, in the development of GBM. These results highlight competitive endogenous RNA networks as alternative molecular therapeutic targets in the treatment of the disease.

摘要

对生物系统进行严格的分子特征分析,揭示了正常和疾病状态下的多种基因变异,以及现存RNA转录本形式的显著复杂性。最近的一个概念,即竞争性内源性RNA,表明一些非编码RNA可以与微小RNA(miRNA)结合,以调节它们在基因表达中的作用。在这里,我们使用了多个平台,整合了信使核糖核酸(mRNA)、非编码RNA和蛋白质数据,以生成一个可能在多形性胶质母细胞瘤(GBM)中失调的RNA-蛋白质网络。利用公开可用的mRNA和miRNA微阵列数据,来鉴定GBM中相对于非肿瘤组织样本差异表达的miRNA和mRNA。基于其预后意义以及它们的靶基因集与维恩图中差异表达基因集的交集,进一步选择靶miRNA。在GBM患者中,两种miRNA,即miR-637和miR-196a-5p,分别与较差和较好的预后相关。非编码RNA,ENSG00000203739/ENSG00000271646和TPTEP1,被预测为miR-637和miR-196a-5p的miRNA靶基因,并与选定的mRNA,CYBRD1和RUFY2呈正相关。使用这两种mRNA构建了一个局部蛋白质相互作用网络。基于ENSG00000203739/ENSG00000271646-miR-637-CYBRD1和TPTEP1-miR-196a-5p-RUFY2调控轴的预测表明,这两种蛋白质在GBM的发生发展中可能分别作为癌基因和肿瘤抑制因子发挥作用。这些结果突出了竞争性内源性RNA网络作为该疾病治疗中替代分子治疗靶点的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a553/7075452/2608eac18179/fonc-10-00303-g0001.jpg

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