MicroRNA As A Novel Blood-based Biomarker For Liver Diseases

The liver is the largest visceral organ in mammals, vulnerable to a variety of pathogens, toxins and immune pathology. Liver diseases have become a common cause of morbidity and mortality. The liver is frequently exposed to many insults as the result of viral infections, alcohol abuse or toxic chemicals overdose. A variety of liver damage caused by harmful factors can be expressed as hepatic necrosis, fatty liver, cholestasis, liver fibrosis, cirrhosis and liver cancer. Prevention and treatment of liver injury is still a serious global issue.Laboratory diagnosis plays a key role for the prevention, diagnosis and treatment of liver diseases. High sensitivity, high-throughput rapid screening techniques are conducive to the timely detection of source of infection, cut off the transmission, to promote the prevention and control of the spread. Extensive research has been conducted to identify more discerning markers in the blood indicating liver damage, but little progress has been achieved in clinical practice. Currently, the level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) present in the blood are the most widely used biochemical markers for hepatocellular damage. It is known that serum AST levels can be elevated in a wide spectrum of clinical disorders. In contrast, elevation in ALT levels is often viewed as a specific indicator of liver necrosis. However, careful literature review reveals that ALT should not be considered a liver-specific marker. Elevated ALT levels are also seen in other clinical conditions, mainly skeletal muscle injury, hypothyroidism or myopathies. These data make the proper differential diagnosis of liver-related diseases based on ALT levels more difficult. Additionally, ALT does not always correlate well with histomorphologic data in clinical application. Thus, several studies have been performed to identify a more specific and reliable marker for liver injury to add information to ALT enzymatic signals. However, progress has been slow and has not led to the development of any better markers than the existing ALT or AST.MicroRNAs (miRNAs) are 21-23 nt long non-coding RNA sequences that are involved in various biological processes, including cell proliferation, cell death, stress resistance, and tumorigenesis. MiRNAs are complementary to 3'UTR sequence motifs that mediate negative post-transcriptional regulation. Affect cell development and disease progression through the up-regulation or the downward expression. A number of miRNAs are specific expression in cells or tissue, so changes in the expression levels of miRNAs may be related to certain diseases patterns. Most attention has been focused on cancer, they thought that the tissue-specific miRNAs are the related molecules on tumor classification and prediction.Recently, circulating miRNAs have been reported as potential biomarkers for the non-invasive diagnosis of cancer. MiRNAs in plasma and serum that are not associated with cells and that are not being degraded by enzymes in the blood that would degrade regular RNA. MiRNAs remain stable even after incubation at room temperature and after many freeze/thaw cycles. These researches show that miRNAs, which weren't previously thought of as markers of cancer in the blood, are a worthwhile class of molecules to study for the purpose of early cancer detection. With the advances in technology, the researches in cycle miRNAs have made substantive progress in cancer diagnosis and prognosis, prenatal diagnosis and other fields.Therefore, the present study was undertaken to investigate whether plasma miRNAs could be used diagnostically to identify liver diseases. A total of 103 patients with chronic hepatitis B viral infections and 15 patients with skeletal muscle disease were recruited into this study. The miRNA expression profile in the plasma of these patients and healthy controls was assessed by real-time quantitative polymerase chain reaction. We also established two mouse model systems, D-galactosamine- and alcohol-induced liver injury, to evaluate whether differential miRNA expression was associated with various types of liver diseases. Among the miRNA candidates identified, miR-122 presented a severity-dependent change in plasma of patients and animal models. Compared to the elevation of aminotransferase in the blood, the change in miR-122 level was detected earlier. Furthermore, this change was more specific for liver injury than for other organ damage and was more reliable, since this change correlated well with liver histological stages.