Identification of ADPKD-Related Key miRNAs by Constructing a miRNA-mRNA Interaction Network and Experimental Verification
Identification of ADPKD-Related Key miRNAs by Constructing a miRNA-mRNA Interaction Network and Experimental Verification
Hui Fang*, Kai Xue and Teng Yang
ABSTRACT
There are many physiological processes that rely on the microRNA-messenger RNA (miRNA-mRNA) network. In this study, an analysis of miRNA-mRNA networks was conducted to identify miRNAs linked to autosomal dominant polycystic kidney disease (ADPKD). Fifty RNA samples from Gene Expression Omnibus (GEO) database were obtained to identify differentially expressed miRNAs (DEMs) and genes (DEGs) in the progression of ADPKD. Functional annotation and enrichment analysis of DEG were performed. iRegulon was used to construct the miRNA-mRNA network and predict related transcription factors (TFs) associated with ADPKD. The function of miRNA network was explored by analyzing GO and KEGG enrichment. Further, qRT-PCR was performed in vitro to determine the expression of miRNAs and mRNAs associated with ADPKD. In the results, 2 DEMs and 1090 DEGs were identified. While DEGs that were downregulated tended to be enriched for metabolic pathways, DEGs that were upregulated tended to be enriched for beta-alanine metabolism, alanine, aspartate, and glutamate metabolism. The miRNA-mRNA network consisted of 2 miRNAs (miR-199a-3p and miR-107) and 7 mRNAs. It appears that miRNAs may positively regulate fibroblast migration, calcium signaling, and cell division based on GO and KEGG analysis. What’s more, by detecting the expression of the key ADPKD-related miRNA-mRNA in vitro experiments, two miRNAs (miR-199a-3p, miR-107) and four candidate target mRNAs (Protein Kinase C Epsilon, PRKCE; Transmembrane P24 Trafficking Protein 5, TMED5; RUNX1 Partner Transcriptional Co-Repressor 1, RUNX1T1; and Fibroblast growth factor 2, FGF2) were identified. In conclusion, ADPKD may be better understood by examining the novel miRNA-mRNA network we constructed.
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