Abstract
Recent studies have demonstrated that micro (mi)RNA molecules can be detected in the circulation and can serve as potential biomarkers of various diseases. This study used microarray analysis to identify aberrantly expressed circulating miRNAs in patients with type 1 autoimmune hepatitis (AIH) compared with healthy controls. Patients with well-documented and untreated AIH were selected from the National Hospital Organization (NHO)-AIH-liver-network database. They underwent blood sampling and liver biopsy with inflammation grading and fibrosis staging before receiving treatment. To further confirm the microarray data, circulating expression levels of miR-21 and miR-122 were quantified by real-time quantitative polymerase chain reaction in 46 AIH patients, 40 patients with chronic hepatitis C (CHC), and 13 healthy controls. Consistent with the microarray data, serum levels of miR-21 were significantly elevated in AIH patients compared with CHC patients and healthy controls. miR-21 and miR-122 serum levels correlated with alanine aminotransferase levels. Circulating levels of miR-21 and miR-122 were significantly reduced in AIH patients with liver cirrhosis, and were inversely correlated with increased stages of fibrosis. By contrast, levels of circulating miR-21 showed a significant correlation with the histological grades of inflammation in AIH. We postulate that aberrantly expressed serum miRNAs are potential biomarkers of AIH and could be implicated in AIH pathogenesis. Alternations of miR-21 and miR-122 serum levels could reflect their putative roles in the mediation of inflammatory processes in AIH.
Highlights
Micro RNAs are small endogenous RNA molecules of 19–24 nucleotides that control the translation and transcription of targeting RNAs by base-pairing to complementary sites [1]
S1 Fig shows the Micro RNAs (miRNAs) that were expressed at higher levels in the sera from autoimmune hepatitis (AIH) patients compared with healthy subjects
The current study provides the first evidence that AIH is associated with altered circulating miRNA expression
Summary
Micro RNAs (miRNAs) are small endogenous RNA molecules of 19–24 nucleotides that control the translation and transcription of targeting RNAs by base-pairing to complementary sites [1]. Serum miRNA expression is stable, reproducible, and consistent among individuals of the same species, and specific expression patterns have been identified as biomarkers for numerous diseases and cancers [2]. MiR-122, the most abundant miRNA in hepatocytes, has a well-defined role in hepatitis C virus (HCV) replication, and serves as a viable therapeutic target [3]. A role for miR-122 is emerging in other liver diseases [4]. MiRNAs regulate the function of both the innate and the adaptive immune system, and altered miRNA expression has been reported in human autoimmune diseases [6]. A unique miRNA expression profile was demonstrated in the sera from an individual with the autoimmune liver disease primary biliary cirrhosis [7]
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