Evolutionary conservation of long non-coding RNAs in non-alcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of conditions ranging from hepatic steatosis to steatohepatitis (NASH) to fibrosis in the absence of alcohol consumption. Its pathogenesis involves both genetic and environmental factors with a multitude of underlying molecular mechanisms and mediators at each stage. Recent transcriptomic-based studies have led to the identification and association of long non-coding RNAs (lncRNAs) with disease pathology in NAFLD patients and in vivo rodent models. However, the knowledge of function of most of the lncRNAs in NAFLD pathology remains obscure. In the current review, we give a comprehensive catalogue of well reported lncRNAs in NAFLD and classify them using sequence and synteny-based evolutionary conservation across rodents, nonhuman primate and human species. The conserved lncRNAs across all the three species may be dissected in larger clinical studies of NAFLD and can be explored as biomarkers and therapeutic targets. In addition, we also review and analyse single nucleotide polymorphisms (SNPs) in these lncRNAs. It adds another facet to the regulatory role of NAFLD-associated lncRNAs and underscores the significance of a novel genetic landscape of non-coding genome in determining the genetic susceptibility of NAFLD.

Keywords: Conservation; Humans; NAFLD; NHPs; Rodents; SNP; lncRNA.