New insights into liver disease diagnosis

New insights into liver disease diagnosis
Narges Pashmforoosh,¹ Masoumeh Baradaran,^2,*
1. Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
2. Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Introduction: Non-coding RNAs are defined as functional RNA molecules that are not translated into proteins. They are involved in regulating of gene expression at the levels of transcription, RNA processing, translation, and protection of genomes from foreign nucleic acids. MicroRNAs are small, non-coding RNAs with a significant role in epigenetic modification that can regulate gene expression in various processes such as development, proliferation, cell signalling, and apoptosis at the post-transcriptional levels. Additionally, miRNAs expression profiles can function as biomarkers of various diseases. microRNA-122 (miR-122) the most frequent microRNA in liver is known as a central regulator of gene networks and pathways in hepatocytes, plays a crucial role in different aspects of hepatic function and in the progress of liver diseases. According to the importance of epigenetics changes in gene expressions during development and differentiation of the various cell types in an organism, in this review, we summarize the current advanced research in epigenetic regulation of miR-122 expression, miR-122 gene targets, and regulatory role of miRNAs in liver physiology and diseases.
Methods: This review involves available literatures about Epigenetic modification roles through specific miRNA (miR-122) in liver diseases such as Hepatocellular carcinoma (HCC), hepatitis C virus (HCV), hepatitis B virus (HBV), Fatty Liver Diseases (ALD/ NAFLD/NASH), Fibrosis, Auto-immune liver disease and liver Iron Homeostasis. Several databases, including PubMed, Web of Science, Science Direct, Springer Link, Wiley Online Library, and Google Scholar databases were searched using a list of suitable keywords obtained from the MeSH to find, collect and classify all relevant data published from January 2000 to March 2020. The number of records identified was 285 and the number of full-length studies included in final analysis was 120.
Results: miR-122 expression is directed by liver-enriched transcription factors (LETFs), such as hepatocyte nuclear factors (HNFs). In most cases, miR-122 can bind with the 3′ un-translated region (UTR) of target mRNAs and mediate repression or induction of the translation of the targets. In hepatocellular carcinoma (HCC) the miR-122 levels are frequently reduced compared with normal liver cells and miR-122 can reduce tumorigenic properties of HCC by targeting several genes involved in tumorigenesis, including ADAM10, Igf1R, SRF, cyclin G1 and ADAM17. While the expression of miR-122 in patients with HBV infection could be significantly decreased, miR-122 is required for HCV replication and mediates this regulation by direct interactions with two binding sites in the 5′UTR of HCV RNA. miR-122 also plays a crucial role in the regulation of cholesterol and fatty acid metabolism in the adult liver. Therefore, a role for it can be considered in fatty liver diseases. In fatty liver disorders, furthermore, mi-RNA-122 is involved in NASH development, such as fatty acid synthase (FAS), and there is a significant increase in the level of mi-RNA-122 in patients with NAFLD and ALD. In hepatic fibrosis, miR-122 is downregulated in activated HSCs and targeting prolyl 4-hydroxylase via miR-122 led to decrease collagen maturation and ECM-production. Therefore, miR-122 along with other microRNAs may potentially serve as a biomarker for diagnosis fibrosis in liver diseases. Autoimmune liver diseases (AIH) is correlated with altered in miRNA expression and it is demonstrated that circulating of miR-122 were significantly elevated in patients. Moreover, miR-122 is involved in controlling systemic iron homeostasis and inhibition of miR-122 caused systemic iron deficiency.
Conclusion: In this systematic review, we have discussed the role of miR-122, the most abundant hepatic miRNA, in liver injuries. Due to the roles of miR-122 in hepatic functions and liver injuries, it can be considered as a sensitive biomarker for liver injuries. Moreover, miR-122 appears to be a promising candidate for effective therapeutic approaches against tumour and infectious diseases of liver. miR-122 may provide a novel strategy to slow down liver disease progression in the future.
Keywords: Epigenetic modification, microRNA, miR-122, Liver diseases, Diagnosis/ Prognosis.