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基于网络的多发性骨髓瘤和意义未明的单克隆丙种球蛋白病分子机制分析。

Network-based analysis of the molecular mechanisms of multiple myeloma and monoclonal gammopathy of undetermined significance.

作者信息

Liu Zhi, Huang Jing, Zhong Qi, She Yanling, Ou Ruimin, Li Cheng, Chen Rui, Yao Mengdong, Zhang Qing, Liu Shuang

机构信息

Department of Hematology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong 510317, P.R. China.

Department of Hematology, The First Hospital of Kashgar District of Xinjiang, Xinjiang 844000, P.R. China.

出版信息

Oncol Lett. 2017 Oct;14(4):4167-4175. doi: 10.3892/ol.2017.6723. Epub 2017 Aug 4.

Abstract

The present study aimed to reveal the molecular mechanisms of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). This was a secondary study on microarray dataset GSE80608, downloaded from the Gene Expression Omnibus database, which included 10 control samples, 10 MGUS samples and 10 MM samples. Differentially expressed genes (DEGs) were identified between control and MGUS samples, and between control and MM samples. A protein-protein interaction (PPI) network was built for studying the interactions between the DEGs. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed for the genes in a gene co-expression network. A microRNA (miRNA/miR)-gene network was built to the evaluate possible the miRNAs and genes involved in the diseases. The present study identified 136 common upregulated DEGs and 165 common downregulated DEGs between MM and MGUS. Pathway enrichment analysis of the genes in the gene co-expression network revealed that the complement and coagulation cascades pathway was significantly enriched for certain complement and coagulation-associated genes. Endothelin-1 (EDN1) was significantly enriched in the hypoxia inducible factor-1 (HIF-1) and tumor necrosis factor signaling pathways. EDN1 was an important node in the PPI network, and a target gene of let-7e, let-7b and miR-19a in the miRNA-gene network. The results of the present study indicate that complement and coagulation-associated genes, the complement and coagulation cascades pathway, EDN1, let-7e, let-7b-5p, miR-19a, and the tumor necrosis factor and HIF-1 signaling pathways may all be implicated in MM and MGUS.

摘要

本研究旨在揭示多发性骨髓瘤(MM)和意义未明的单克隆丙种球蛋白病(MGUS)的分子机制。这是一项对从基因表达综合数据库下载的微阵列数据集GSE80608进行的二次研究,该数据集包括10个对照样本、10个MGUS样本和10个MM样本。在对照样本与MGUS样本之间以及对照样本与MM样本之间鉴定出差异表达基因(DEG)。构建了蛋白质-蛋白质相互作用(PPI)网络以研究DEG之间的相互作用。对基因共表达网络中的基因进行京都基因与基因组百科全书通路富集分析。构建了一个微小RNA(miRNA/miR)-基因网络以评估可能参与这些疾病的miRNA和基因。本研究在MM和MGUS之间鉴定出136个共同上调的DEG和165个共同下调的DEG。对基因共表达网络中的基因进行的通路富集分析表明,补体和凝血级联反应通路因某些补体和凝血相关基因而显著富集。内皮素-1(EDN1)在缺氧诱导因子-1(HIF-1)和肿瘤坏死因子信号通路中显著富集。EDN1是PPI网络中的一个重要节点,并且是miRNA-基因网络中let-7e、let-7b和miR-19a的靶基因。本研究结果表明,补体和凝血相关基因、补体和凝血级联反应通路、EDN1、let-7e、let-7b-5p、miR-19a以及肿瘤坏死因子和HIF-1信号通路可能均与MM和MGUS有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad9f/5592848/6913e117b87f/ol-14-04-4167-g00.jpg

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