miRNAs, lncRNAs, circRNAs and piRNAs in Nonalcoholic Fatty Liver Disease: Past, Present and Future.

Nowadays, nonalcoholic fatty liver disease (NAFLD) represents the most common cause of chronic liver disorder worldwide. From the clinical point of view, it evolves from steatosis to nonalcoholic steatohepatitis, which can lead to cirrhosis and finally to hepatocellular carcinoma. The mechanisms involved in its progression to more pathological stages and NAFLD pathogenesis are not completely understood. The research concerning NAFLD has become urgent and important because the age of NAFLD diagnosis is progressively decreasing, and its relationship with cancer risk is already well known. Because NAFLD ultimately leads to disability and imposes a major socioeconomic burden, timely diagnosis and effective treatment of NAFLD is particularly important. In the development of NAFLD, noncoding RNAs (ncRNAs) represented by microRNAs, long noncoding RNAs, circular RNAs, and piRNAs are epigenetic factors that play important regulatory roles. In the current review, we present updated information regarding the role of miRNAs, lncRNAs, circRNAs, and piRNAs, aiming to develop a good understanding of their regulatory functions in hepatic metabolism and concerning their potential use as biomarkers for early NAFLD/NASH diagnosis and as therapeutic targets.