Parallel expression profiling of hepatic and serum microRNA-122 associated with clinical features and treatment responses in chronic hepatitis C patients

Abstract

MicroRNAs (miRNAs) are small, non-coding RNAs that regulate a variety of biological processes. Recently, human liver-specific miRNA miR-122 has been reported to facilitate hepatitis C virus (HCV) replication in liver cells. HCV is one of the leading causes of liver diseases worldwide. In Pakistan, the estimated prevalence is up to 10%. Here, we report hepatic and serum miR-122 expression profiling from paired liver and serum samples from treatment-naive chronic hepatitis C (CHC) patients and controls. We aimed to elucidate the biomarker potential of serum miR-122 for monitoring disease progression and predicting end treatment response (ETR). Hepatic miR-122 levels were significantly down-regulated in CHC patients. A significant inverse correlation was observed between hepatic and serum miR-122 levels, indicating that serum miR-122 levels reflect HCV-associated disease progression. Both hepatic and serum miR-122 were significantly correlated (P < 0.05) with several clinicopathological features of CHC. Receiver operator curve analysis showed that serum miR-122 had superior discriminatory ability even in patients with normal alanine transaminase levels. Multivariate logistic regression analysis highlighted pre-treatment serum miR-122 levels as independent predictors of ETR. In conclusion, serum miR-122 holds the potential to serve as a promising biomarker of disease progression and ETR in CHC patients.

Hepatitis C virus direct‐acting antivirals therapy impacts on extracellular vesicles microRNAs content and on their immunomodulating properties

“…In order to assess whether DAA therapy could impact on HCV‐EXO miRNA content, a longitudinal study was performed on selected patients (n = 10) by quantifying miRNAs levels at T0 and 6 months after DAA therapy (T6). As expected, in all patients, the exosomal levels of the liver‐specific miR‐122‐5p showed a significant decrease (Figure ). Interestingly, a consistent reduction was also observed in the immunomodulatory miRNAs miR‐222‐3p, miR‐146a‐5p, miR‐150‐5p, miR‐30c, miR‐378a‐3p and miR‐20a‐5p.…”

“…Hepatitis C virus (HCV) profoundly affects the hepatic and circulating miRNAs expression patterns, in particular of the liver‐specific miR‐122‐5p, known to be instrumental for HCV replication . Furthermore, miR‐122‐5p serum level have proved to correlate with viral load and to viral clearance . In this line of research, the expression dynamics of hepatic microRNAs has recently been associated to the immunological status of patients and to their response to treatment .…”

MiR‐122 modification enhances the therapeutic efficacy of adipose tissue‐derived mesenchymal stem cells against liver fibrosis

“…Genetic manipulation, which aims to produce therapeutic genes, enhances the therapeutic abilities of MSCs . MiR‐122 is down‐regulated in the livers of patients with primary biliary cirrhosis and chronic HCV‐induced fibrosis and in the livers of mice treated with CCl 4 ; moreover, miR‐122 plays a critical role in liver fibrosis by negatively regulating the proliferation and transactivation of HSCs . Thus, targeted delivery of miR‐122 into liver, particularly in HSCs, is a potential novel strategy for enhancing the therapeutic effect of MSCs on liver fibrosis.…”

Circulating miR-122 levels in self-recovering hepatitis E patients

“…This is the first preliminary study exploring association, if any, of miR-122 with HEV infection. Availability of biopsied liver samples collected for routine diagnosis allowed miR-122 studies in liver/serum samples of chronic hepatitis B and C patients [27][28][29]. However, HE being predominantly a self-recovering infection, our study is restricted to circulating miRNA levels.…”