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Profiling of miRNAs involved in liver carcinogenesis by age [CH]

ABSTRACT: Previous studies have identified several microRNAs (miRNAs) that may coordinate multiple pathways associated with age-related carcinogenesis. We compared hepatic miRNA expression patterns in chronic hepatitis (CH) and hepatocellular carcinoma (HCC) to elucidate age-related differences potentially underlying hepatocarcinogenesis. 2565 miRNAs in 360 liver tissues specimens were analyzed.

ORGANISM(S): Homo sapiens

PROVIDER: GSE147887 | GEO | 2020/06/20

REPOSITORIES: GEO

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Project description:Background & aims: The role of microRNAs (miRNAs) in Alcoholic Hepatitis (AH) and their potential as therapeutic targets in liver disease has not been explored yet. This study aims at profiling miRNA in AH and identifying dysregulated miRNAs involved in AH pathophysiology. Methods: miRNA expression arrays were performed in 13 AH, 5 alcohol liver disease-induced cirrhosis (ALD-CH), 5 nonalcoholic steatohepatitis induced cirrhosis (NASH-CH), 4 HCV-induced cirrhosis (HCV-CH) and 6 non-injured liver control samples. Genome wide expression profile was retrieved for 12 paired AH and control samples. MiRNA and mRNA expression data was integrated and identified miRNAs were validated in AH samples and in animal models of liver injury. Results:Â The miRNA array showed 111 upregulated and 66 downregulated miRNAs in AH versus healthy subjects. The comparison of miRNA profile in liver samples from AH among ALD-CH, HCV-CH and NASH-CH identified 18 miRNAs specifically dysregulated in AH. Integrative miRNA and mRNA analysis in AH identified dysregulated miRNAs for which their target genes were also dysregulated. A functional analysis of identified miRNAs and their targets revealed their involvement in the regulation of canonical pathways related to apoptosis, fatty acid metabolism and cell cycle among others. miRNAs expression (miR-182, miR-21, miR-155, miR-214, miR-432, miR-422a) was validated in an independent cohort of AH. MiR-182 expression correlated with cholestasis, disease severity and short-term mortality. Moreover, miR-182 expression is associated to cholestasis with ductular reaction but not to fibrosis and inflammation in animal models of liver injury. Conclusions:Â AH is characterized by an important dysregulation of miRNA expression with a unique miRNA profile. MiRNAs specifically expressed in AH are associated to cholestasisâ¦ Uncovered miRNAs are involved in important pathophysiological features in AH suggesting ta regulation of he role of miRNAs in the regulation of AH, and highlight miR-182 as a potential regulator of its pathophysiology. miRNA expression arrays were performed in 13 AH(Alcoholic hepatitis), 5 alcohol liver disease-induced cirrhosis (ALD-CH), 5 nonalcoholic steatohepatitis induced cirrhosis (NASH-CH), 4 HCV-induced cirrhosis (HCV-CH) and 6 non-injured liver control samples(CTRL).

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Profiling of miRNAs involved in liver carcinogenesis by age [CH]

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