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参与特发性肺纤维化的枢纽微小RNA-枢纽基因相互作用网络分析及其在非小细胞肺癌中的新作用

Analysis of the Interaction Network of Hub miRNAs-Hub Genes, Being Involved in Idiopathic Pulmonary Fibers and Its Emerging Role in Non-small Cell Lung Cancer.

作者信息

Yu Dong Hu, Ruan Xiao-Lan, Huang Jing-Yu, Liu Xiao-Ping, Ma Hao-Li, Chen Chen, Hu Wei-Dong, Li Sheng

机构信息

Department of Biological Repositories, Zhongnan Hospital, Wuhan University, Wuhan, China.

Department of Hematology, Renmin Hospital, Wuhan University, Wuhan, China.

出版信息

Front Genet. 2020 Apr 2;11:302. doi: 10.3389/fgene.2020.00302. eCollection 2020.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a fibrotic interstitial lung disease with lesions confined to the lungs. To identify meaningful microRNA (miRNA) and gene modules related to the IPF progression, GSE32537 (RNA-sequencing data) and GSE32538 (miRNA-sequencing data) were downloaded and processed, and then weighted gene co-expression network analysis (WGCNA) was applied to construct gene co-expression networks and miRNA co-expression networks. GSE10667, GSE70866, and GSE27430 were used to make a reasonable validation for the results and evaluate the clinical significance of the genes and the miRNAs. Six hub genes (COL3A1, COL1A2, OGN, COL15A1, ASPN, and MXRA5) and seven hub miRNAs (hsa-let-7b-5p, hsa-miR-26a-5p, hsa-miR-25-3p, hsa-miR-29c-3p, hsa-let-7c-5p, hsa-miR-29b-3p, and hsa-miR-26b-5p) were clarified and validated. Meanwhile, iteration network of hub miRNAs-hub genes was constructed, and the emerging role of the network being involved in non-small cell lung cancer (NSCLC) was also analyzed by several webtools. The expression levels of hub genes were different between normal lung tissues and NSCLC tissues. Six genes (COL3A1, COL1A2, OGN, COL15A1, ASPN, and MXRA5) and three miRNAs (hsa-miR-29c-3p, hsa-let-7c-5p, and hsa-miR-29b-3p) were related to the survival time of lung adenocarcinoma (LUAD). The interaction network of hub miRNAs-hub genes might provide common mechanisms involving in IPF and NSCLC. More importantly, useful clues were provided for clinical treatment of both diseases based on novel molecular advances.

摘要

特发性肺纤维化(IPF)是一种纤维化间质性肺疾病,病变局限于肺部。为了识别与IPF进展相关的有意义的微小RNA(miRNA)和基因模块,下载并处理了GSE32537(RNA测序数据)和GSE32538(miRNA测序数据),然后应用加权基因共表达网络分析(WGCNA)构建基因共表达网络和miRNA共表达网络。使用GSE10667、GSE70866和GSE27430对结果进行合理验证,并评估基因和miRNA的临床意义。阐明并验证了六个枢纽基因(COL3A1、COL1A2、OGN、COL15A1、ASPN和MXRA5)和七个枢纽miRNA(hsa-let-7b-5p、hsa-miR-26a-5p、hsa-miR-25-3p、hsa-miR-29c-3p、hsa-let-7c-5p、hsa-miR-29b-3p和hsa-miR-26b-5p)。同时,构建了枢纽miRNA-枢纽基因的迭代网络,并通过几个网络工具分析了该网络在非小细胞肺癌(NSCLC)中的新作用。正常肺组织和NSCLC组织中枢纽基因的表达水平不同。六个基因(COL3A1、COL1A2、OGN、COL15A1、ASPN和MXRA5)和三个miRNA(hsa-miR-29c-3p、hsa-let-7c-5p和hsa-miR-29b-3p)与肺腺癌(LUAD)的生存时间有关。枢纽miRNA-枢纽基因的相互作用网络可能提供涉及IPF和NSCLC的共同机制。更重要的是,基于新的分子进展为这两种疾病的临床治疗提供了有用的线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f352/7142269/7cbb2326cdef/fgene-11-00302-g001.jpg

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