Construction of miRNA-mRNA Regulatory Network and Prognostic Signature in Endometrial Cancer

This bioinformatic study confirmed a new miRNA-mRNA regulatory network and a prognostic signature in endometrial cancer (EC). We downloaded RNA-seq and miRNA-seq data of EC from the TCGA database, then used EdegR package to screen differentially expressed miRNAs and mRNAs (DE-miRNAs and DE-mRNAs). T...

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Bibliographic Details
Published in:OncoTargets and therapy 2021-01, Vol.14, p.2363-2378
Main Authors: Sun, Rui, Liu, Jinhui, Nie, Sipei, Li, Siyue, Yang, Jing, Jiang, Yi, Cheng, Wenjun
Format: Article
Language:English
Subjects:
Cancer
Cancer therapies
Cell cycle
Cell growth
Chromosome 5
Connective tissue growth factor
Dendritic cells
Endometrial cancer
Endometrium
Gene expression
Genes
Infiltration
Lymphocytes
Medical prognosis
Messenger RNA
MicroRNA
MicroRNAs
miRNA
mRNA
Myc protein
Nomograms
Original Research
Proteins
Regression analysis
Software
Survival analysis
Transcription factors
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Summary:This bioinformatic study confirmed a new miRNA-mRNA regulatory network and a prognostic signature in endometrial cancer (EC). We downloaded RNA-seq and miRNA-seq data of EC from the TCGA database, then used EdegR package to screen differentially expressed miRNAs and mRNAs (DE-miRNAs and DE-mRNAs). Then, we constructed a regulatory network of EC-associated miRNAs and hub genes by Cytoscape, and determined the expression of unexplored miRNAs in EC tissues and normal adjacent tissues by quantitative Real-Time PCR (qRT-PCR). A prognostic signature model and a predictive nomogram were constructed. Finally, we explored the association between the prognostic model and the immune cell infiltration. A total of 11,531 DE-mRNAs and 236 DE-miRNAs, as well as 275 and 118 candidate DEGs for upregulated and downregulated DE-miRNAs were screened out. The miRNA-mRNA network included 5 downregulated and 13 upregulated DE-miRNAs. qRT-PCR proved that the expression levels of miRNA-18a-5p, miRNA-18b-5p, miRNA-449c-5p and miRNA-1224-5p and their target genes (NR3C1, CTGF, MYC, and TNS1) were consistent with our predictions. Univariate and multivariate Cox proportional hazards regression analyses of the hub genes revealed a significant prognostic value of NR3C1, EZH2, AND GATA4, and these genes were closely related to eight types of immune infiltration cells. We identified three genes as candidate biomarkers for EC, which may provide a theoretical basis for targeted therapy.
ISSN:1178-6930
1178-6930
DOI:10.2147/OTT.S272222