MicroRNA-146a regulates the transformation from liver fibrosis to cirrhosis in patients with hepatitis B via interleukin-6.

The aim of the present study was to measure the expression of microRNA (miR)-146a in liver tissues, peripheral blood mononuclear cells (PMBC) and serum from patients with Hepatitis B and either liver fibrosis or cirrhosis, as well as to determine the regulatory mechanism of miR-146a. A total of 36 patients with Hepatitis B and liver fibrosis and 25 patients with hepatitis B and liver cirrhosis admitted to Linyi People's Hospital (Shandong, China) between June 2012 and February 2016 were included in the present study. Reverse transcription-quantitative polymerase chain reaction was performed to determine the expression of miR-146a and interleukin (IL)-6 mRNA in the liver tissue, PBMCs and serum. Western blotting was used to assess the expression of IL-6 in liver tissues and PBMCs. An enzyme-linked immunosorbent assay was conducted to measure IL-6 levels in serum. To identify the direct interaction between IL-6 and miR-146a, a dual luciferase reporter assay was performed. IL-6 mRNA expression in liver tissues, PBMCs and serum from patients with liver cirrhosis was significantly higher than that from patients with liver fibrosis (P<0.05). Furthermore, IL-6 expression in liver tissues and PBMCs from patients with liver cirrhosis was enhanced and levels of IL-6 protein in the serum of patients with liver cirrhosis were significantly elevated compared with patients with liver fibrosis (P<0.05). By contrast, levels of miR-146a in liver tissues, PBMCs and serum from patients with liver cirrhosis were significantly downregulated (P<0.05) compared with patients with liver fibrosis. miR-146a regulated the expression of IL-6 by binding to its 3'-untranslated region. Thus, in the transformation from liver fibrosis to cirrhosis, the upregulation of IL-6 in liver tissues, PBMCs and serum may be associated with the downregulation of miR-146a. miR-146a directly targets IL-6, which may regulate the occurrence and immune responses of Hepatitis B.