Angiopoietin-like 8 (ANGPTL8) expression is regulated by miR-143-3p in human hepatocytes

Abstract

Angiopoietin-like protein 8 (ANGPTL8) is associated with reduced HDL-cholesterol levels and may contribute to the development of dyslipidemia. Factors regulating ANGPTL8 expression remain poorly understood. Here we analyzed the relationship between miRNA-143-3p and ANGPTL8 in liver cells. Using target prediction algorithms, we identified a putative binding site for miR-143-3p in the ANGPTL8 3' untranslated region (3'UTR). Exogenous miR-143-3p interacted with the ANGPTL8 3'UTR to downregulate its expression compared to scrambled sequence control. Transfection of HepG2 cells with miR-143-3p mimic or siRNA resulted in decreased or increased ANGPTL8 transcript and protein levels, respectively. Treatment of HepG2 cells with 30 mM glucose, 100 nM insulin, or 75 ng/ml lipopolysaccharide to mimic hyperglycemic, hyperinsulinemic, and proinflammatory conditions corresponded with increased miR-143-3p and ANGPTL8 levels. Inhibition of miR-143-3p amplified ANGPTL8 response to these treatments, suggesting that the miRNA acts to suppress ANGPTL8 expression under metabolically distorted conditions. These results, combined with growing evidence supporting a role for ANGPTL8 in the regulation of HDL-C metabolism, provide a better understanding of the molecular mechanisms underlying ANGPTL8 expression.

Keywords: Angiopoietin-like protein 8; Atherosclerosis; Betatrophin; HDL-C; Hyperglycemia; Inflammation; miRNA, miR-143-3p; microRNA.