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. (H epatology 2016;64:58‐72)