Circulating Liver-Specific miR-122 as a Novel Potential Biomarker for Diagnosis of Cholestatic Liver Injury

Abstract

BackgroundCirculating microRNA-122 (miR-122) has been increasingly reported to be a potential biomarker for drug-, viral-, alcohol- and chemical-induced liver injury. The present study was initiated to determine the potential of circulating miR-122 as a biomarker for cholestatic liver injury.MethodsBoth bile-duct ligation (BDL) mice and patients with biliary calculi were employed as cholestatic liver injury models, and serum miR-122 level was determined by stem-loop real-time reverse-transcription PCR (SLqRT-PCR). All quantitative PCR values were normalized to those for U6 RNA and calculated with the 2−△Ct method.ResultsSerum miR-122 increased significantly after BDL-induced cholestatic injury and showed a similar time course to ALT concentrations. Compared with the sham controls, BDL mice had increased serum levels of miR-122 by 24.36±12.86, 423.63±322.89, 4.43±2.02 and 12.23±8.92 folds after 1, 3, 7 and 14 days, respectively. Moreover, serum miR-122 level was substantially higher in patients with biliary calculi than that in the healthy control group. In addition, patients with severe liver injury showed significantly higher levels of serum miR-122 when compared with healthy controls or patients with mild or moderate liver injury. Furthermore, serum miR-122 was found to show significant diagnostic value for biliary calculi by yielding an AUC (the areas under the receiver operating characteristic curve) of 0.931 with 77.4% sensitivity and 96.4% specificity in discriminating biliary calculi from healthy controls.ConclusionCollectively, these data suggest that serum miR-122 has strong potential as a novel, specific and noninvasive biomarker for diagnosis of cholestasis-induced liver injury.

Micro RNAs mir‐106a, mir‐122 and mir‐197 are increased in severe acute viral hepatitis with coagulopathy

“…In this study, we found that patients with severe acute viral hepatitis, who displayed high ALT, AST and bilirubin levels as well as an abnormal prothrombin time, showed significantly higher serum levels of mir‐122 than patients with moderate hepatitis. These data are in accordance with previous findings and confirm that the mir‐122 serum level might reflect the inflammatory activity and the amount of injury in the liver . Our data also correspond to recent findings from John et al .…”

MicroRNA expression patterns and signalling pathways in the development and progression of childhood solid tumours

“…Serum levels of miR-122-5p were increased, while the expression of miR-122-5p was reduced in liver tissue, which could be due to passive miRNA drainage from tumour cells, as has been observed in other tumours [123]. Expression of miR-122-5p has been identified as a non-specific marker of liver damage, and is increased in the serum of jaundiced patients [124]. These studies highlight the importance of identifying miRNA profiles (in tumour tissue and in serum), and shows that there may be specific miRNAs with unique roles in various types of childhood solid tumours.…”

Serum miRNA‐122 in acute liver injury induced by kidney injury and sepsis in CD‐1 mouse models

“…Currently, alanine transaminase (ALT), also known as the serum glutamic‐pyruvic transaminase, is the predominant hepatocyte enzyme that is routinely used to detect liver injury . Another novel biomarker that was recently used to detect liver injury is miRNA‐122 (miR‐122) . miRNA (miR), a single‐stranded RNA, regulates the functions of mRNA including the interference of post‐translational gene regulation procedures such as the degradation of the mRNA and the blockade of the translation processes .…”

“…miR‐122 is abundantly expressed on hepatocytes and responsible for several hepatic‐involved pathways such as the liver lipid metabolism, hepatitis C amplification and interferon antiviral responses, hepatocellular carcinoma development and hepatocyte apoptosis . Circulating miR‐122 is a sensitive biomarker that can be used to detect early hepatic injury from several causes such as drugs, alcohol, bile salts, chemical substances and viruses . Recently, circulating miR‐122 was tested in a human pilot study for detecting liver damage .…”