基于高通量芯片对急性髓系白血病竞争内源性RNA网络的构建和分析

doi:10.13481/j.1671-587X.20210317

Abstract

Abstract:

Objective： To construct a network of competitive endogenous RNA （ceRNA） associated with acute myeloid leukemia （AML），and to explore the molecular mechanism of occurrence and development of AML.

Methods

The expression matrix of AML （GSE96535） was downloaded from NCBI Gene Expression Database （GEO）.The differentially expressed mRNA and long non-coding RNAs（lncRNAs） were screened using the edgeR package of R language. miRcode， miRDB， miRTarBase ，and TargetScan databases were used to predict the regulatory relationships between the differentially expressed lncRNA and miRNA， and the differentially expressed mRNA and miRNA. Cytoscape software was utilized for the construction of the ceRNA regulatory network of lncRNA-miRNA-mRNA.Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） were performed to conduct the enrichment analysis of the differentially expressed genes. The core gene， Hub gene， was screened by using CytoHubba plug-in. The GEPIA database was used to compare the expressions of the top 10 Hub genes in the AML patients and normal controls， and then the survival curve of Hub gene was plotted.

Results

Compared with normal controls，a total of 1 105 mRNAs and 387 lncRNAs were differentially expressed in the AML patients. The constructed lncRNA-miRNA-mRNA ceRNA regulatory network consisted of 45 lncRNAs， 31 miRNAs and 89 mRNAs.The GO analysis results showed that the differentially expressed genes were mainly concentrated in the membrane microdomain and glutamate receptor binding， and regulated epithelial cell proliferation.The KEGG analysis results revealed that 19 pathways were enriched， including transcriptional regulation， proteoglycan regulation， and Ras signaling pathway. GATA binding protein 3（GATA3），WT1 transcription factor （WT1）， peroxisome proliferator activated receptor gamma （PPARG） and other top 10 Hub genes with the highest connectivity were screened by CytoHubba. The GEPIA database was performed to verify that GATA3， WT1， MYB proto-oncogene （MYB）， SRY-box transcription factor 4（SOX4） and E2F7 had the differential expression levels. Moreover， the survival rate of the patients in E2F7 low-expression group was higher than that in E2F7 high-expression group（P=0.028）.

Conclusion

The screened ceRNA network composed of lncRNA， miRNA and mRNA may promote the occurrence and development of AML.

Key words: bioinformatics, acute myeloid leukemia, competitive endogenous RNA, gene chip

CLC Number:

R733.7

Yuqing PAN, Yunyan SUN, Yixun LI, Liying WANG, Zhuoma SINAN, Rui CHEN, Xi ZHANG, Yan DU. Construction and analysis of competitive endogenous RNA networks in acute myeloid leukemia based on high-throughput microarray[J].Journal of Jilin University(Medicine Edition), 2021, 47(3): 669-676.

Figures/Tables 6

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Construction and analysis of competitive endogenous RNA networks in acute myeloid leukemia based on high-throughput microarray

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