Circulating RNA Molecules as Biomarkers in Liver Disease

Abstract

Liver disease is a major cause of morbidity and mortality worldwide. As in other fields of medicine, there is a stringent need for non-invasive markers to improve patient diagnostics, monitoring and prognostic ability in liver pathology. Cell-free circulating RNA molecules have been recently acknowledged as an important source of potential medical biomarkers. However, many aspects related to the biology of these molecules remain to be elucidated. In this review, we summarize current concepts related to the origin, transportation and possible functions of cell-free RNA. We outline current development of extracellular RNA-based biomarkers in the main forms of non-inherited liver disease: chronic viral hepatitis, hepatocellular carcinoma, non-alcoholic fatty liver, hepato-toxicity, and liver transplantation. Despite recent technological advances, the lack of standardization in the assessment of these markers makes their adoption into clinical practice difficult. We thus finally review the main factors influencing quantification of circulating RNA. These factors should be considered in the reporting and interpretation of current findings, as well as in the proper planning of future studies, to improve reliability and reproducibility of results.

Molecular Regulation of Mirnas and Potential Biomarkers in the Progression of Hepatic Steatosis to NASH

“…Among of these nine, miR-182, miR-31, miR-183, miR-224 and miR-150 were upregulated, while miR-590, miR-378i, miR-17 and miR-219a were downregulated [57]. Moreover, miR-122, the most extensively studied liver specific miRNA, was reported to be significantly decreased in steatohepatitis in the fibrotic liver of mouse fed with methionine-choline-deficient after eight week [58] and demonstrated correlation with the grade of severity of the steatosis [59].…”

Circulating miRNA or circulating DNA—Potential biomarkers for organ transplant rejection

“…Plasma miRNA measurements can be used to monitor tissue damage in the liver, muscle, and brain . For instance, miR‐122 is the hepatocyte‐specific miRNA; it can be used as a noninvasive biomarker for a wide range of clinical liver‐specific diseases . Furthermore, increased miRNA expression (miR‐122, miR‐148a, and miR‐194) has been observed in the serum of patients with liver injury induced by rejection; they are positively correlated with transaminase levels in liver transplant recipients .…”

Translational Prospects and Challenges in Human Induced Pluripotent Stem Cell Research in Drug Discovery

“…MiR-122 constitutes approximately 70% of all microRNAs expressed in hepatocytes, and an increase in circulating miR-122 in serum plasma has been shown to correlate with and even precede the typical increase in ALT levels after DILI [100]. Interestingly, increased level of circulating hepatic miR-122 was reported to correlate well with the severity of progression of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) [54,101,102]. …”