基于microrna表达谱的骨髓增生异常综合征中microrna的鉴定和综合分析

IF 0.4 Q4 MEDICINE, RESEARCH & EXPERIMENTAL Precision Medical Sciences Pub Date : 2021-12-01 DOI:10.1002/prm2.12054
Limin Ma, Haiping Yang, Xuewen Yang
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引用次数: 0

摘要

骨髓增生异常综合征(MDS)是一组恶性血液病,其特征是造血干细胞发育异常,并增加患急性粒细胞白血病的风险。尽管MDS的发病机制尚不完全清楚,但据报道,MDS中存在各种微小RNA(miRNA)的改变。本研究旨在通过对miRNA表达谱的综合生物信息学分析,探讨MDS的分子机制。GSE81372表达谱数据集是从基因表达综合数据库下载的。鉴定MDS和正常对照之间差异表达的miRNA(DEM),并预测miRNA的靶点。随后,对靶基因进行了基因本体论(GO)功能和途径富集分析。最后,构建并分析了通路关系网络和miRNA-GO调控网络。共鉴定出6个上调和35个下调的DEM。结果表明,DEMs的靶基因主要参与信号转导、凝血、凋亡、细胞增殖、跨膜转运和血管生成等过程。显著富集的途径包括MAPK信号通路、PI3K-Akt信号通路、TGF-β信号通路、Hippo信号通路和P53信号通路。此外,miR-195-5p、miR-4505、miR-22-3p和miR-148a-3p被选为miRNA-GO调节网络中的枢纽miRNA,它们的异常表达可能与MDS的发病机制密切相关。我们的发现提供了MDS中被破坏的miRNA和途径的登记,这有可能在临床上用于MDS的诊断和靶向治疗。
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Identification and integrative analysis of microRNAs in myelodysplastic syndromes based on microRNAs expression profile
Myelodysplastic syndromes (MDS) are a group of malignant hematological disorders characterized by the abnormal development of hematopoietic stem cells and increased risk of acute myelogenous leukemia. Although the pathogenesis of MDS has not been fully understood, various alterations of microRNAs (miRNAs) have been reported in MDS. This study aimed to explore the molecular mechanisms of MDS by integrative bioinformatics analysis of miRNAs expression profile. The GSE81372 expression profile dataset was downloaded from Gene Expression Omnibus database. The differentially expressed miRNAs (DEMs) between MDS and normal controls were identified and targets of miRNAs were predicted. Subsequently, gene ontology (GO) functional and pathway enrichment analyses of target genes were performed. Finally, pathway relation network and miRNA–GO regulatory network were constructed and analyzed. A total of six upregulated and 35 downregulated DEMs were identified. The results showed that target genes of DEMs mainly participated in the process of signal transduction, blood coagulation, apoptotic process, cell proliferation, transmembrane transport, and angiogenesis. The significantly enriched pathways included MAPK signaling pathway, PI3K‐Akt signaling pathway, TGF‐beta signaling pathway, Hippo signaling pathway, and P53 signaling pathway. Moreover, miR‐195‐5p, miR‐4505, miR‐22‐3p, and miR‐148a‐3p were selected as hub miRNAs in miRNA–GO regulatory network and their aberrant expression might be closely associated with MDS pathogenesis. Our discovery provides a registry of miRNAs and pathways that are disrupted in MDS, which has the potential to be used in clinic for diagnosis and target therapy of MDS in future.
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来源期刊
Precision Medical Sciences
Precision Medical Sciences MEDICINE, RESEARCH & EXPERIMENTAL-
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0.00%
发文量
33
审稿时长
15 weeks
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