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microRNA changes in liver tissue associated with fibrosis progression in patients with hepatitis C
Kendall R Van Keuren-Jensen1, Ivana Malenica1, Amanda L Courtright1
1Neurogenomics, Translational Genomics Research Institute, Phoenix, AZ, USA.
Background & Aims:
Accumulating evidence indicates that microRNAs play a role in a number of disease processes including the pathogenesis of liver fibrosis in hepatitis C infection. Our goal is to add to the accruing information regarding microRNA deregulation in liver fibrosis to increase our understanding of the underlying mechanisms of pathology and progression.
Methods:
We used next generation sequencing to profile all detectable microRNAs in liver tissue and serum from patients with hepatitis C, stages F1-F4 of fibrosis.
Results:
We found altered expression of several microRNAs, in particular, miR-182, miR199a-5p, miR-200a-5p and miR-183 were found to be significantly upregulated in tissue from liver biopsies of hepatitis C patients with advanced fibrosis, stage F3 and F4, when compared with liver biopsies from patients with early fibrosis, stages F1 and F2. We also found miR-148-5p, miR-1260b, miR-122-3p and miR-378i among the microRNAs most significantly down-regulated from early to advanced fibrosis of the liver. We also sequenced the serum microRNAs; however, we were not able to detect significant changes in circulating microRNAs associated with fibrosis stage after adjusting for multiple tests.
Conclusions:
Adding measurements of tissue microRNAs acquired during routine biopsies will continue to increase our knowledge of underlying mechanisms of fibrosis. Our goal is that these data, in combination with studies from other researchers and future long-term studies, could be used to enhance the staging accuracy of liver biopsies and expand the surveillance of patients at increased risk for cancer and progression to advanced fibrosis.
Insights
MicroRNAs are altered in hepatitis C liver fibrosis. Specific microRNAs like miR-182 and miR-199a-5p are upregulated in advanced fibrosis, while others are downregulated, offering potential for improved diagnostics.
Area of Science:
- Hepatology
- Molecular Biology
- Genomics
Background:
- MicroRNAs (miRNAs) are implicated in liver fibrosis pathogenesis in hepatitis C virus (HCV) infection.
- Understanding miRNA deregulation is crucial for elucidating fibrosis mechanisms and progression.
Purpose of the Study:
- To investigate microRNA expression profiles in liver tissue and serum of patients with varying stages of liver fibrosis due to HCV.
- To identify specific miRNAs associated with the progression of liver fibrosis.
Main Methods:
- Next-generation sequencing was employed to profile all detectable microRNAs.
- Analysis included liver tissue and serum samples from patients with hepatitis C and fibrosis stages F1-F4.
Main Results:
- Several miRNAs showed altered expression in liver tissue. Notably, miR-182, miR-199a-5p, miR-200a-5p, and miR-183 were significantly upregulated in advanced fibrosis (F3-F4) compared to early stages (F1-F2).
- Conversely, miR-148-5p, miR-1260b, miR-122-3p, and miR-378i were significantly downregulated with fibrosis progression.
- No significant changes in circulating serum microRNAs were detected after statistical adjustment.
Conclusions:
- Tissue microRNA measurements from biopsies can enhance understanding of fibrosis mechanisms.
- These findings may contribute to improved liver biopsy staging accuracy and surveillance for cancer risk and advanced fibrosis progression.
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