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Background <p>Nonalcoholic steatohepatitis (NASH) pathogenesis involves apoptosis, inflammation, lipogenesis, and insulin resistance. Hepatocyte apoptosis leads to liver injury and fibrosis, while inflammation exacerbates damage through immune cells and cytokines. Lipogenesis promotes fat accumulation and lipotoxicity, stressing hepatocytes, whereas insulin resistance impairs glucose metabolism and exacerbates dysfunction. Highlight the complexity of NASH and the need for multi-targeted therapies are highlighted by these interrelated processes. Using in silico transcriptomic analysis, this study identifies key microRNAs (miRNAs) in NASH and explores the relationship between miRNAs and circ-MYO9B in NASH.</p> Methods <p>To find differentially expressed miRNAs (DEMs), miRNA expression profiles from the liver and blood datasets (GSE33857, GSE59492, and GSE49012) were examined. Nonalcoholic steatohepatitis-induced cirrhosis (NASH-CH)-related miRNA modules were discovered by Weighted Gene Co-expression Network Analysis (WGCNA). RT-qPCR was used on tissue and blood samples to examine the expression and interaction of circ-MYO9B and hsa-miR-193b-5p in NASH patients, and dual-luciferase assays confirmed their direct interaction.</p> Results <p>Circ-MYO9B and hsa-miR-193b-5p were found to be significantly correlated in both blood and liver tissue in NASH-CH patients, according to expression analysis. RT-qPCR analysis validated their dysregulation, suggesting their role in the advancement of the disease. The direct interaction between circ-MYO9B and hsa-miR-193b-5p was confirmed by the dual-luciferase assay, indicating a regulatory function in metabolic pathways.</p> Conclusions <p>By modulating this miRNA, circ-MYO9B may influence downstream pathways in which miR-193b-5p is known to be involved, such as lipogenesis, inflammation, apoptosis, and glucose metabolism. These findings suggest that circ-MYO9B may represent a potential therapeutic target for addressing metabolic dysfunction associated with NASH, although further validation in hepatocyte-specific models is warranted.</p>

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Circ-MYO9B modulates metabolic pathways in nonalcoholic steatohepatitis via miR-193b-5p

  • 期刊论文

  • 发表日期：

    2025年11月4日

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  • Mohammad Ebrahim Golchin,
  • Siavash Rahimian Chaleshtori,
  • Mahboobeh Golchin,
  • Azam Shiasi,
  • Fatemeh Amirsoleimani,
  • Nasrin Fattahi Dolatabadi

摘要

Background

Nonalcoholic steatohepatitis (NASH) pathogenesis involves apoptosis, inflammation, lipogenesis, and insulin resistance. Hepatocyte apoptosis leads to liver injury and fibrosis, while inflammation exacerbates damage through immune cells and cytokines. Lipogenesis promotes fat accumulation and lipotoxicity, stressing hepatocytes, whereas insulin resistance impairs glucose metabolism and exacerbates dysfunction. Highlight the complexity of NASH and the need for multi-targeted therapies are highlighted by these interrelated processes. Using in silico transcriptomic analysis, this study identifies key microRNAs (miRNAs) in NASH and explores the relationship between miRNAs and circ-MYO9B in NASH.

Methods

To find differentially expressed miRNAs (DEMs), miRNA expression profiles from the liver and blood datasets (GSE33857, GSE59492, and GSE49012) were examined. Nonalcoholic steatohepatitis-induced cirrhosis (NASH-CH)-related miRNA modules were discovered by Weighted Gene Co-expression Network Analysis (WGCNA). RT-qPCR was used on tissue and blood samples to examine the expression and interaction of circ-MYO9B and hsa-miR-193b-5p in NASH patients, and dual-luciferase assays confirmed their direct interaction.

Results

Circ-MYO9B and hsa-miR-193b-5p were found to be significantly correlated in both blood and liver tissue in NASH-CH patients, according to expression analysis. RT-qPCR analysis validated their dysregulation, suggesting their role in the advancement of the disease. The direct interaction between circ-MYO9B and hsa-miR-193b-5p was confirmed by the dual-luciferase assay, indicating a regulatory function in metabolic pathways.

Conclusions

By modulating this miRNA, circ-MYO9B may influence downstream pathways in which miR-193b-5p is known to be involved, such as lipogenesis, inflammation, apoptosis, and glucose metabolism. These findings suggest that circ-MYO9B may represent a potential therapeutic target for addressing metabolic dysfunction associated with NASH, although further validation in hepatocyte-specific models is warranted.