MicroRNA and hepatitis C virus- challenges in investigation and translation: a review of the literature

Abstract

Investigations into the role of microRNA (miRNA) in hepatitis C virus (HCV) infection, disease pathogenesis and host immune and treatment response have potential to produce innovations in diagnosis, prognosis and therapy. However, investigational challenges remain in generating clinically useful and reproducible results. We review the literature with a primary emphasis on methods and technologies used to construct our current understanding of miRNA and HCV disease. A second emphasis is to understand potential clinical research applications and provide clarification of previous study results. Many miRNA have key roles in viral and immunopathogenesis of HCV infection across multiple tissue compartments. Controversy exists among published studies regarding relative measurements, temporal changes and biological significance of specific miRNA and HCV infection. To reconcile diverging data, additional research into optimal sample processing, in vitro models, techniques for microarray differential expression of miRNAs, practices for sample result normalization, and effect of HCV genotype variation on expression are all necessary. Microarray and miRNA isolation techniques should be selected based on ability to generate reproducible results in the sample type of interest. More direct comparisons of efficacy and reliability of various multiplex microarrays and an improved consensus around miRNA normalization and quantitation are necessary so that data can be compared across studies.

Serum and exosomal miR‐122 and miR‐199a as a biomarker to predict therapeutic efficacy of hepatitis C patients

“…Circulating miR122 has been investigated as a biomarker in HCV therapy is currently underway . Although serum miR‐122 levels correlated with changes in HCV levels across all genotypes, miR‐122 was significantly higher in HCV genotype 1b patients than in non‐genotype 1b patients in our study, indicating that the viral genotype might be a key factor that provokes changes in miRNA expression . Our results reveal that serum miR‐122 levels are closely related to therapy outcomes, suggesting that miR‐122 expression correlate with the treatment response .…”

“…Investigations into the role of miRNA in HCV infection, disease pathogenesis and host immune and treatment response have the potential to produce innovations in diagnosis, prognosis and therapy . Circulating miR122 has been investigated as a biomarker in HCV therapy is currently underway .…”

“…Note that the differences in HCV genotypes may have large implications in the relevance of specific miRNA. Studies using patient samples should note their viral genotypes and, whenever possible, compare samples within genotypes instead of across genotypes . In addition, it will be important to investigate the differences in miRNA expression based on gender, race, and age, which are likely to be confounders when generalizing the study results …”

“…Emerging studies have revealed the roles of microRNA (miRNA) in HCV propagation and pathogenesis. Viral genotype may be a key factor in provoking changes in miRNA expression, and genotype‐specific effects on replicon systems may also confound generalizability . microRNA‐122 (miR‐122), the most abundant miRNA (comprises 70% of the total miRNAs) in the liver, regulates metabolic pathways, including cholesterol biosynthesis, fatty acid synthesis, and oxidation.…”

Inhibition of microRNA-199a-5p reduces the replication of HCV via regulating the pro-survival pathway

“…Unfortunately, no effective strategies have met the urgent need for HCV treatment. Recently, accumulating studies have highlighted the importance of cellular miRNAs in regulating HCV pathogenesis due to their versatility (Waldron and Holodniy, 2014). miR-199a-5p, a mature form of miR-199a, has been found to be effective in the inhibition of human hepatocellular carcinoma (Shen et al, 2010), in promoting liver repopulation (Mobus et al, 2014) and in hepatocyte protection (Dai et al, 2013), but little is known regarding its efficacy in HCV treatment.…”