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Global micro RNA expression profiling in the liver biopsies of Hepatitis B Virus infected patients suggests specific miRNA signatures for viral persistence and hepatocellular injury.
Singh, Avishek Kumar Rooge, Sheetalnath Babasaheb Varshney, Aditi Vasudevan, Madavan Bhardwaj, Ankit Venugopal, Senthil Kumar Trehanpati, Nirupama Kumar, Manoj Kumar, Vijay
Singh, Avishek Kumar
Rooge, Sheetalnath Babasaheb
Varshney, Aditi
Vasudevan, Madavan
Bhardwaj, Ankit
Venugopal, Senthil Kumar
Trehanpati, Nirupama
Kumar, Manoj
Kumar, Vijay
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2017-11-30
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Abstract
Hepatitis B virus (HBV) can manipulate the miRNA regulatory networks in infected cells to create a permissive environment for viral replication, cellular injury, disease onset and its progression. The aim of the present study was to understand the miRNA networks and their target genes in the liver of hepatitis B patients involved in HBV replication, liver injury and liver fibrosis. We investigated differentially expressed miRNAs by microarray in the liver biopsy samples from different stages of HBV infection and liver disease [immune tolerant (IT; n= 8); acute viral hepatitis (AVH; n=8); no fibrosis (n=16); early (F1+F2) (n=19) or late fibrosis (F3+F4) (n=14) and healthy controls (n=7)]. The miRNA expression levels were analyzed by the unsupervised principal component analysis (PCA) and hierarchical clustering. Analysis of miRNA-mRNA regulatory networks identified 17 miRNAs and 18 target gene interactions with four distinct nodes each representing a stage-specific gene regulation during disease progression. The IT group showed elevated miR-199a-5p, miR-221-3p and Let-7a-3p levels which could target genes involved in innate immune response and viral replication. In AVH group, miR-125b-5p and miR-3613-3p were up whereas miR-940 was down which might affect cell proliferation via STAT3 pathway. In early fibrosis, miR-34b-3p, miR-1224-3p and miR-1227-3p were up while miR-499a-5p was down which together, possibly mediate chronic inflammation. In advanced fibrosis, miR-1, miR-10b-5p, miR-96-5p, miR-133b and miR-671-5p were up while miR-20b-5p and miR-455-3p were down, possibly allowing chronic disease progression. Interestingly, only 8 of 17 liver-specific miRNAs exhibited a similar expression pattern in patient sera.
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Global micro RNA expression profiling in the liver biopsies of Hepatitis B Virus infected patients suggests specific miRNA signatures for viral persistence and hepatocellular injury. 2017 Hepatology
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en
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1527-3350