Non-coding RNA therapeutics: Towards a new candidate for arsenic-induced liver disease

Arsenic, a metalloid toxicant, has caused serious environmental pollution and is presently a global health issue. Long-term exposure to arsenic causes diverse organ and system dysfunctions, including liver disease. Arsenic-induced liver disease comprises a spectrum of liver pathologies, ranging from hepatocyte damage, steatosis, fibrosis, to hepatocellular carcinoma. Various mechanisms, including an imbalance in redox reactions, mitochondrial dysfunction and epigenetic changes, participate in the pathogenesis of arsenic-induced liver disease. Altered epigenetic processes involved in its initiation and progression. Dysregulated modulations of non-coding RNAs (ncRNAs), including miRNAs, lncRNAs and circRNAs, exert regulating effects on these processes. Here, we have reviewed the underlying pathogenic mechanisms that lead to progressive arsenic-induced liver disease, and we provide a discussion focusing on the effects of ncRNAs on dysfunctions in intercellular communication and on the activation of hepatic stellate cells and malignant transformation of hepatocytes. Further, we have discussed the roles of ncRNAs in intercellular communication via extracellular vesicles and cytokines, and have provided a perspective for the application of ncRNAs as biomarkers in the early diagnosis and evaluation of the pathogenesis of arsenic-induced liver disease. Further investigations of ncRNAs will help us to understand the nature of arsenic-induced liver disease and to identify biomarkers and therapeutic targets.