miR-146a通过IL-6调控乙型肝炎肝纤维化向肝硬化转化的机制研究

Abstract

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