miR-34a promotes liver fibrosis in patients with chronic hepatitis via mediating Sirt1/p53 signaling pathway

Purpose: This research aimed to explore the correlation between miR-34a expression in peripheral blood and clinical characteristics of patients with chronic hepatitis C (CHC) as well as the diagnostic and prognostic values of serum miR-34a in CHC. Methods: Serum samples of 41 CHC patients and 18 normal participants were collected to examine the expression levels of miR-34a using qRT-PCR. The changes of serum TBA, liver enzyme AST and ALT were also determined by enzyme colorimetry and rate method. The levels of serum fibrotic markers hyaluronic acid (HA), type III procollagen (PCIII), type IV collagen (IV-C) and laminin (LN) were detected by radioimmunoassay. Degree of liver fibrosis was examined by liver biopsy. Western blot analysis was used to investigate the expression of ac-p53, p53 and Sirt1 in the liver tissues of CHC patients. Results: MiR-34a was significantly increased in the serum of CHC patients than that in healthy participants, and serum miR-34a was correlated with liver fibrosis index. Serum TBA, AST and ALT levels, and AST/ALT ratios in patients with CHC were increased with increasing degree of fibrosis, and were positively associated with serum miR-34a. Furthermore, the liver tissues of CHC patients showed low Sirt1 protein expression and highly ac-p53 protein expression. Conclusions: Serum miR-34a in patients with CHC could promote liver fibrosis through mediating the Sirt1/p53 pathway and might function as pivotal biomarker on the prognosis and diagnosis of CHC patients.