NF‐κB‐upregulated miR‐155‐5p promotes hepatocyte mitochondrial dysfunction to accelerate the development of nonalcoholic fatty liver disease through downregulation of STC1

Abstract

Previous studies have highlighted the involvement of nuclear factor kappa B (NF‐κB) in the development of nonalcoholic fatty liver disease (NAFLD). The purpose of our investigation is to explore the interaction among NF‐κB, microRNA‐155‐5p (miR‐155‐5p), and Stanniocalcin 1 (STC1), and its effects on NAFLD by establishing a NAFLD model in Sprague Dawley rats. A highly‐expressed miR‐155‐5p and NF‐κB was revealed in the liver tissues of NAFLD rats, and a positive correlation was identified between miR‐155‐5p and NF‐κB. Next, the expression of NF‐κB and STC1 was altered in the modeled rats through lentivirus injection, followed by determination on the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, triglycerides, and low‐density lipoprotein cholesterol. Furthermore, the hepatocyte mitochondria were separated to measure the activities of adenosine triphosphate (ATP), reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and mitochondrial respiratory chain complex, and to observe the number, length and ultrastructural length of mitochondrial cristae. The results demonstrated that NF‐κB overexpression induced mitochondrial dysfunction, increased ROS level, decreased ATP and MMP contents, as well as inhibited the number and length of mitochondrial cristae in the hepatocyte mitochondria of NAFLD rats. Besides, miR‐155‐5p was found to negatively regulate STC1 expression based on dual luciferase reporter gene assay, which exert inhibition on mitochondrial activity of hepatocytes in NAFLD rats. These results uncover the possible involvement of NF‐κB/miR‐155‐5p/STC1 axis in NAFLD progression, that NF‐κB could increase miR‐155‐5p expression to inhibit STC1 expression, thus inducing hepatic mitochondrial dysfunction and promoting the occurrence and development of NAFLD.

Herbal medicine Huazhuo Tiaozhi granule ameliorates dyslipidemia via regulating DDX17 lactylation and miR-155-5p biogenesis

“…In the present study, we discovered that HTG refreshed the liver miRNA pro le in dyslipidemia rats, especially rno-miR-155-5p. MiR-155-5p was found to be highly-expressed in the liver tissues of NAFLD rats and promoted NAFLD progression [14] . On the other hand, miR-155-5p regulated cholesterol e ux and ameliorate atherosclerosis [15][16] Here, we elucidated that HTG administration disrupted miR-155-5p expression and lipid accumulation in hepatocytes.…”

Herbal medicine formula Huazhuo Tiaozhi granule ameliorates dyslipidaemia via regulating histone lactylation and miR-155-5p biogenesis

“…In the present study, we found that HTG restored the liver miRNA profile in dyslipidaemic rats, especially that of rno-miR-155-5p. MiR-155-5p was found to be highly expressed in the liver tissues of NAFLD rats and to promote NAFLD progression [18]. Moreover, miR-155-5p regulates cholesterol efflux and promotes atherosclerosis [19,20].…”

Investigating the Role of Non-Coding RNA in Non-Alcoholic Fatty Liver Disease

“…The expression of LncARSR correlates with the activated state of PI3K/AKT/ mTOR pathway [99] miR-155 Upregulated These ncRNASs have an influence on the induction of inflammation via NF-κB pathway [100,101] Platr4 Upregulated [102] LncTNF Upregulated [103] miR-125 Upregulated…”

“…Studies have shown that activated NF-κB can induce or inhibit miRNA expression. Shen et al showed a correlation between increased miR-155 expression and active NF-κB levels in NAFLD-rat model, suggesting that NF-κB could induce miR-155 expression and enhance inflammation [100]. Furthermore, it has been reported that miR-155 hampers the expression of several transcripts that act as a TNF-α suppressor [101].…”