Computational identification of microRNAs and their targets in liver cirrhosis.

Abstract

Previous studies have revealed that the deregulation of circulating miRNAs is associated with liver cirrhosis. The present study aimed to identify reliable candidate biomarkers to improve the early detection of liver cirrhosis. An integrated analysis of expression profiles of microRNAs (miRNAs/miRs) and mRNAs in liver cirrhosis tissues from the GEO database was performed. Next, the regulatory targets of the differentially expressed miRNAs in liver cirrhosis tissues were predicted. In addition, a regulatory network of miRNA-target genes was constructed. A total of 4 eligible mRNA expression profiling studies and 2 miRNA expression profiling studies met the inclusion criteria, and were thus included. A total of 48 differentially expressed miRNAs and 1,773 differentially expressed genes were identified in liver cirrhosis tissues compared with normal tissues. There were 240 miRNA-target pairs whose expression was negatively correlated. In the miRNA-target regulatory network, overexpression of miR-21 and miR-199a-3p was suggested to be closely associated with the progression of liver cirrhosis. In addition, functional enrichment analysis of the target genes indicated that cell cycle was the most significantly enriched pathway, and the dysregulation of leukemia inhibitory factor, cancerous inhibitor of protein phosphatase 2A and retinoblastoma-associated protein 1 clearly suggested their importance in the development of liver cirrhosis. We hypothesized that miR-21 and miR-199a-3p may be promising non-invasive diagnostic biomarkers for the early diagnosis of liver cirrhosis. The miRNA-target regulatory network may provide additional insight into the current data regarding the role of miRNAs in liver cirrhosis.