A Novel Long Noncoding RNA Lnc-HC Binds hnRNPA2B1 to Regulate Expressions of Cyp7a1 and Abca1 in Hepatocytic Cholesterol Metabolism

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Abstract

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 namedlnc-HCnegatively regulating cholesterol metabolism within hepatocytes through physical interaction with hnRNPA2B1. By further binding to the target messenger RNA ofCyp7a1orAbca1, thelnc-HC-hnRNPA2B1 complex decreases expressions of the two genes that are implicated in cellular cholesterol excretion.lnc-HCknockdown can strongly recover the cholesterol disorderin vivo. In the upstream pathway,lnc-HCis up-regulated by high cholesterol by the transcription activator, CCAAT/enhancer-binding protein beta.

Conclusion:

These findings suggest a subtle feed-forward regulation oflnc-HCin 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)

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