The Role of Long Non-Coding RNAs (lncRNAs) in the Development and Progression of Fibrosis Associated with Nonalcoholic Fatty Liver Disease (NAFLD)

Abstract

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of conditions ranging from hepatic steatosis to inflammation (nonalcoholic steatohepatitis or NASH) with or without fibrosis, in the absence of significant alcohol consumption. The presence of fibrosis in NASH patients is associated with greater liver-related morbidity and mortality; however, the molecular mechanisms underlying the development of fibrosis and cirrhosis in NAFLD patients remain poorly understood. Long non-coding RNAs (lncRNAs) are emerging as key contributors to biological processes that are underpinning the initiation and progression of NAFLD fibrosis. This review summarizes the experimental findings that have been obtained to date in animal models of liver fibrosis and NAFLD patients with fibrosis. We also discuss the potential applicability of circulating lncRNAs to serve as biomarkers for the diagnosis and prognosis of NAFLD fibrosis. A better understanding of the role played by lncRNAs in NAFLD fibrosis is critical for the identification of novel therapeutic targets for drug development and improved, noninvasive methods for disease diagnosis.

Keywords: epigenetics; hepatic carcinoma; liver fibrosis; long non-coding RNA; nonalcoholic fatty liver disease (NAFLD); nonalcoholic steatohepatitis (NASH).

Figure 1

Stages of nonalcoholic fatty liver disease (NAFLD). Liver appearance in the various stages of the disease is schematized to represent the physical changes that accompany disease progression. The percentage of patients progressing from one stage to the subsequent stage is depicted below the arrows. NASH: nonalcoholic steatohepatitis, HCC: hepatocellular carcinoma.