MiR-98-5p as a novel biomarker suppress liver fibrosis by targeting TGFβ receptor 1.

Abstract

Hepatic fibrosis is the repair reaction of excessive deposition and abnormal distribution of extracellular matrix after various liver injuries, especially chronic HBV infection, which is a key step in the development of various chronic liver diseases to cirrhosis. Recent studies have showed that microRNAs (miRNAs) can regulate a series of liver fibrosis-related gene express and play an important role in the development of liver fibrosis. But the miRNAs expression profiling and the differentially expressed miRNAs in patients with HBV-related liver fibrosis were little known. This study aims to have a record of a systemic screening for liver fibrosis-associated miRNAs in patients infected with HBV. A IlluminaHiSeq sequencing of plasma miRNAs from the HBV-related liver fibrosis patients (S2/3, n = 8) based on Scheuer's staging criteria and from healthy volunteers 42 (n = 7) was performed. Cluster analysis and target gene prediction were performed for the differentially expressed miRNAs. Gene ontology (GO) analysis and KEGG pathway enrichment analysis also were performed on the differentially expressed target miRNA genes. Compared with the healthy control group, 77 miRNAs were screened out from the liver fibrosis group, among which 51 miRNAs were up-regulated and 26 miRNAs were down-regulated. Eventually, miR-98-5p was identified as a candidate predictor of liver fibrosis progression. miR-98-5p is reduced in activated LX2 cells, and miR-98-5p overexpression inhibited the HSCs activation. Mechanically, MiR-98-5p prevents liver fibrosis by targeting TGFbR1 and blocking TGFb1/Smad3 signaling pathway. Furthermore, serum miR-98-5p levels were measured from a total of 70 recruited patients with chronic HBV infection and 29 healthy individuals as controls. Serum miR-98-5p level was significantly lower in patients with liver fibrosis than in healthy controls and HBV carriers. The expression of miRNAs in patients with liver fibrosis is significantly different from that of healthy volunteers. Many signal pathways of hepatic fibrosis are regulated by miRNAs. The potential value of miR-98-5p is as diagnostic biomarkers and therapeutic targets for HBV-related liver fibrosis.