Upregulated microRNA-199a-5p inhibits nuclear receptor corepressor 1 translation in mice with non-alcoholic steatohepatitis

Abstract

Abstract. Mounting evidence indicates that dysregulated microRNAs (miRNAs) are important in the etiology and pathogenesis of steatohepatitis. However, the functions of miRNAs in the pathophysiological process of non-alcoholic steatohepatitis (NASH) are poorly understood. In this study, C57BL/6J mice were fed a methionine-choline-deficient (MCD) diet for eight weeks in order to induce hepatic steatohepatitis. Using reverse transcription polymerase chain reaction, the hepatic expression levels of miR-199a-5p, miR-122 and miR-221 in the mice were examined. Bioinformatic analysis of dysregulated miR-199a-5p was performed to predict the potential role of miR-199a-5p in NASH. The MCD diet was found to significantly reduce miR-122 expression levels and significantly increase miR-199a-5p expression levels in mouse livers, compared with those of mice fed a control diet. In the bioinformatic analysis, miR-199a-5p was identified to be predominantly involved in transcription, protein serine/threonine kinase activity, insulin signaling, and the Wnt and mitogen-activated protein kinase signaling pathways. The regulation of nuclear receptor corepressor 1 (NCOR1) by miR-199a-5p was also examined by silencing and overexpressing this miRNA in LX-2 cells. The data revealed that NCOR1 protein levels were significantly reduced and enhanced by miR-199a-5p mimic and inhibitor, respectively. These findings suggest a key role for miR-199a-5p in the progression of NASH through inhibition of NCOR1 translation, and provide novel insights into NASH pathogenesis.

Integrative proteomic and microRNA analysis of the priming phase during rat liver regeneration

“…Research findings showed miR-199a was identified to be predominantly involved in transcription, insulin and mitogen-activated protein kinase signaling pathways, and could inhibit cell proliferation of human HCC (Jia et al, 2012;Zhang et al, 2014). In our study, we found that the level of miR-199a was increased at 2 h after PH.…”

Effect of miR-146 targeted HDMCP up-regulation in the pathogenesis of nonalcoholic steatohepatitis

“…Decreased miR-144 and miR-451 were found in NASH, where the former elicits and the latter inhibits proinflammatory cytokine production by respectively targeting TLR-2 [29]and AMPK/AKT pathway [30]. In contrast, increased miR-199a-5p was found in NASH by inhibiting nuclear receptor corepressor 1 translation[31]. Based on our microarray data of NASH rat model [20] and bioinformatics prediction (Fig 5A), we selected miR-146, miR-29b and miR-10ato detect their levels in NASH model.…”

Role of microRNAs on the Regulation of Mitochondrial Biogenesis and Insulin Signaling in Skeletal Muscle

“…Furthermore, RIP140 mRNA contains a large 3′ UTR of ∼3.5 kb that remains to be investigated for target sites of additional miRNAs (Rosell et al, ). The levels of NCOR1 protein were significantly changed by miR‐199a‐5p (Zhang et al, ). These studies provide evidence for miRNAs to maintain metabolic homeostasis by regulating the levels of co‐repressors and their transcriptional output.…”