miR-122 – A key factor and therapeutic target in liver disease

Abstract

Being the largest internal organ of the human body with the unique ability of self-regeneration, the liver is involved in a wide variety of vital functions that require highly orchestrated and controlled biochemical processes. Increasing evidence suggests that microRNAs (miRNAs) are essential for the regulation of liver development, regeneration and metabolic functions. Hence, alterations in intrahepatic miRNA networks have been associated with liver disease including hepatitis, steatosis, cirrhosis and hepatocellular carcinoma (HCC). miR-122 is the most frequent miRNA in the adult liver, and a central player in liver biology and disease. Furthermore, miR-122 has been shown to be an essential host factor for hepatitis C virus (HCV) infection and an antiviral target, complementary to the standard of care using direct-acting antivirals or interferon-based treatment. This review summarizes our current understanding of the key role of miR-122 in liver physiology and disease, highlighting its role in HCC and viral hepatitis. We also discuss the perspectives of miRNA-based therapeutic approaches for viral hepatitis and liver disease.

The Role of Circulating MicroRNAs as Markers of Disease Progression in Hepatitis C Virus Infected Egyptian Patients

“…The discrepancies between different studies may arise from variability in technical procedures from sampling, or the use of different normalization controls or control tissues used for normalization (healthy liver or adjacent non-tumor tissue) [32] or may be due to the small patient population [33].…”

“…However, we found a negative correlation of miRNA-122 with serum HCV RNA, matching with Marquez et al [21] who found that miRNA-122 expression was altered in HCV-infected liver, and miRNA-122 level was inversely correlated, with viral load, fibrosis and serum liver transaminase levels. A possible explanation for this inverse relation is that, counter-intuitively, the beneficial role of miRNA-122 for the virus in vitro does not translate into a positive correlation between its expression and HCV load in patients [33].…”

Addition of coconut oil to the diet based on maize dried distilled grains with solubles (DDGS) alters miR-122a expression in the pig liver

“…miR-122a was extensively studied after the discovery that it may modulate Hepatitis C Virus (HCV) mRNA expression, making it a potential target for antiviral intervention (Jopling et al, 2005). It has been shown that miR-122a is engaged in many liver diseases, like cancer, hepatitis, steatosis and cirrhosis (Bandiera et al, 2015). Furthermore, miR-122a is associated with various metabolic processes, including cholesterol metabolism.…”

The possible role of NS3 protease activity of hepatitis C virus on fibrogenesis and miR-122 expression in hepatic stellate cells

“…Previous studies have shown that miRNA-122 expression could be decreased in Huh7.5.1 cells transfected with HCV core protein, which corresponds with our results emphasizing the possible role of miR-122 in fibrogenesis and liver cirrhosis Ezzat et al, 2014). Furthermore, other studies in mouse HSCs have shown that the overexpression of miRNA-122 reduced the collagen level, and lower ECM deposition is an indicator of less liver fibrosis related diseases (Jopling, 2008;Bandiera et al, 2015). Furthermore, our achievements also indicated that, while both versions of NS3 proteins downregulated miR-122, a measurable difference between protease competent and protease mutated forms was observed as is indicated by the more but not fully dependent role of protease in this function (P >0.01).…”