Elucidation of novel miRNA candidates and their role in unraveling the pathology of Non-Alcoholic Fatty Liver Disease

Abstract

Non-Alcoholic Fatty Liver Disease (NAFLD) is a chronic liver disease which is observed in people who do not abuse alcohol. Main cause of NAFLD is Non-Alcoholic Steatohepatitis (NASH) where there is accumulation of fats such as triglyceride in liver and the disease progression ranges from simple steatosis to fibrosis and cirrhosis. MicroRNAs are critical players in post-transcriptional gene regulation of diseases with complex etiology. In this study, we have elucidated the role of microRNAs (miRNAs) in the pathophysiology of NAFLD/NASH and unravelled molecular markers for diagnosis of NAFLD. A subset of genes (n=10) responsible for NAFLD/NASH were selected and detailed in silico analysis carried out using multiple tools. miRDB and DIANA-microT were used to find putative miRNA binding sites followed by analysis using miRTarBase which is an experimentally validated database of miRNA-target interactions. The study elucidated a number of statistically significant predictions for both miRDB (scores >80) and DIANA-microT (values >0.90) and also strong experimental validation in miRTarBase. The analysis revealed that certain miRNAs like miR-7 & miR-548 family members are found in both the programmes, miRDB and DIANA-microT, targeting genes involved in liver function. They were also identified in the experimental validation database miRTarBase. These miRNAs probably play an important role in the pathophysiology of this disease. They can also be used as prognostic/diagnostic markers for assessment of NAFLD.