A novel long noncoding RNA Lnc HC binds hnRNPA2B1 to regulate expressions of Cyp7a1 and Abca1 in hepatocytic cholesterol metabolism
Cholesterol metabolism disorder in hepatocytes predicts a higher risk of metabolic syndrome (MetS) Long noncoding RNAs (lncRNAs) have emerged as critical players in cellular cholesterol metabolism, but their functions are not systematically clarified. Here, we have identified a novel lncRNA named lnc HC negatively regulating cholesterol metabolism within hepatocytes through physical interaction with hnRNPA2B1. By further binding to the target messenger RNA of Cyp7a1 or Abca1, the lnc HC hnRNPA2B1 complex decreases expressions of the two genes that are implicated in cellular cholesterol excretion. lnc HC knockdown can strongly recover the cholesterol disorder in vivo. In the upstream pathway, lnc HC is up regulated by high cholesterol by the transcription activator, CCAAT/enhancer binding protein beta. Conclusion: These findings suggest a subtle feed forward regulation of lnc HC in cholesterol metabolism and define a novel line of evidence by which lncRNAs modulate the metabolic system at the post transcriptional level. (Hepatology 2016;64:58 72)
Hepatology