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Comprehensive profiling of serum microRNAs in normal and non-alcoholic fatty liver disease (NAFLD) patients
Jian-Wei Zhang1,2, Kamran Ullah3, Nauman Khan4
1Shaoxing Maternity and Child Health Care Hospital, No. 222 Fenglin East Road, Shaoxing, 312000, Zhejiang, China.
Insights
Pediatric non-alcoholic fatty liver disease (NAFLD) is linked to altered microRNA (miRNA) levels, particularly miR-122-5p, impacting liver and heart health. Targeting miR-122 may offer therapeutic benefits for NAFLD patients at risk of cardiovascular disease.
Area of Science:
- Biochemistry
- Genetics
- Cardiology
Background:
- Pediatric non-alcoholic fatty liver disease (NAFLD) is a growing global health issue with severe long-term consequences, including cirrhosis, liver cancer, and cardiovascular disease.
- The underlying pathological mechanisms of NAFLD involve functional differences in microRNAs (miRNAs), which are small non-coding RNA molecules that regulate gene expression.
- Serum exosomal miRNAs may reflect liver pathology and systemic metabolic changes, while serum miRNAs can indicate broader physiological processes.
Purpose of the Study:
- To identify differentially expressed miRNAs in the serum of pediatric NAFLD patients compared to healthy controls.
- To investigate the role of specific miRNAs, particularly miR-122-5p, in the progression of NAFLD and its associated cardiovascular risks.
- To explore potential therapeutic targets for NAFLD and its complications.
Main Methods:
- RNA sequencing was employed to profile miRNA expression in serum samples from pediatric NAFLD patients and controls.
- Quantitative real-time PCR (qRT-PCR) was used for validation of differentially expressed miRNAs, including miR-122-5p.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to understand the functional roles of identified miRNAs.
Main Results:
- Thirty-six miRNAs exhibited differential expression in pediatric NAFLD patients, with 21 upregulated and 15 downregulated compared to controls.
- Serum miR-122-5p levels were significantly upregulated in NAFLD patients, consistent with previous exosomal miRNA findings.
- Functional analysis indicated that differentially expressed miRNAs are involved in various biological processes, and miR-122-5p plays a crucial role in cardiovascular function, potentially through the miR-122/Sirt-6/ACE2 axis, contributing to myocardial necrosis.
Conclusions:
- miR-122 is implicated in the progression of pediatric NAFLD and associated metabolic disturbances, increasing cardiovascular disease risk.
- The miR-122/Sirt-6/ACE2 axis may be a key pathway in NAFLD-related myocardial damage.
- Targeting miR-122 presents a promising therapeutic strategy for improving both hepatic and cardiac outcomes in pediatric NAFLD.
Abstract:
Pediatric non-alcoholic fatty liver disease (NAFLD) is emerging as a worldwide health concern with the potential to advance to cirrhosis and liver cancer. NAFLD can also directly contribute to heart problems through inflammation and insulin resistance, even in individuals without other risk factors. The pathological mechanisms of NAFLD are linked to functional differences of miRNAs in different biological environments. The miRNA in serum exosomes may reflect the pathological state of the liver and changes in systemic metabolism, while the miRNA in serum may be associated with physiological processes other than the liver. Pediatric non-alcoholic fatty liver disease (NAFLD) is emerging as a worldwide health concern with the potential to advance to cirrhosis and liver cancer. NAFLD can also directly contribute to heart problems through inflammation and insulin resistance, even in individuals without other risk factors. The pathological mechanisms of NAFLD are linked to functional differences of miRNAs in different biological environments. The miRNA in serum exosomes may reflect the pathological state of the liver and changes in systemic metabolism, while the miRNA in serum may be associated with physiological processes other than the liver. Pediatric non-alcoholic fatty liver disease (NAFLD) is emerging as a worldwide health concern with the potential to advance to cirrhosis and liver cancer. NAFLD can also directly contribute to heart problems through inflammation and insulin resistance, even in individuals without other risk factors. The pathological mechanisms of NAFLD are linked to functional differences of miRNAs in different biological environments. The miRNA in serum exosomes may reflect the pathological state of the liver and changes in systemic metabolism, while the miRNA in serum may be associated with physiological processes other than the liver. Our study identified 36 miRNAs with differential expression in the serum of NAFLD patients compared to the control group, including 21 miRNAs with significantly increased expression and 15 with decreased expression. Consistent with our previously reported data on serum-derived exosomal miRNA profiling, this study also observed a notable upregulation of serum miR-122-5p levels in NAFLD patients. PCR validation confirmed the differential expression of miR-122-5p identified through RNA sequencing. Functional analysis using GO and KEGG pathways revealed a diverse range of biological roles associated with these differentially expressed miRNAs. Notably, NAFLD significantly impacts heart health, with miR-122-5p playing a key role in regulating cardiovascular function. Furthermore, activation of the miR-122/Sirt-6/ACE2 axis may contribute to myocardial necrosis, highlighting its potential role in NAFLD-associated cardiovascular risks. Our study suggests that miR-122 plays a key role in the progression of NAFLD and its associated metabolic disturbances, which can increase the risk of cardiovascular disease. Targeting miR-122 may offer potential therapeutic benefits for improving both liver and heart health in individuals with NAFLD.
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