CircularRNA as novel biomarkers in liver diseases

The liver is an essential organ that is primarily responsible for digestion and eliminating toxic substances from the body. After the industrial revolution, Western diet and lifestyle changes have increased the incidence of several liver diseases, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma (HCC). NAFLD and NASH are mostly asymptomatic at early stages, and the disease progression from NAFLD to life-threatening HCC remains not fully understood. Circular RNA (circRNA) is consist of a circular structure, and the circRNA-microRNA(miRNA)-mRNA axes have been shown to be involved in several cellular events, including apoptosis, vascularization, metastasis, etc. The highly stable structure of circRNAs has enabled themselves to be used as putative biomarkers of several diseases. Here, we conducted a literature review and discussed the identified roles of circRNAs in NAFLD, NASH, liver cirrhosis, and HCC. For example, deficiency of circRNA_0046366 and circRNA_0046367 has been shown as the characteristics of NAFLD, and restoration of these circRNAs ameliorates the oxidative stress, lipotoxicity, and disease severity in NAFLD. Silencing of circ_0071410 was shown to alleviate hepatic stellate activation, the key step of liver cirrhosis. CDR1 and circ_0067934 can facilitate the invasion and metastasis of HCC, while circMTO1 negatively regulates the progression of HCC. Although several research works have been conducted, the whole picture of circRNA-related underlying mechanisms is unclear. Future works using high-throughput bioinformatic approaches will be needed to delineate the role of circRNAs in liver diseases and to further develop novel diagnostics and therapeutics.