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A novel long noncoding RNA Lnc‐HC binds hnRNPA2B1 to regulate expressions of Cyp7a1 and Abca1 in hepatocytic cholesterol metabolism
Author(s) -
Lan Xi,
Yan Jidong,
Ren Juan,
Zhong Bo,
Li Jing,
Li Yue,
Liu Li,
Yi Jing,
Sun Qingzhu,
Yang Xudong,
Sun Jian,
Meng Liesu,
Zhu Wenhua,
Holmdahl Rikard,
Li Dongmin,
Lu Shemin
Publication year - 2016
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.28391
Subject(s) - cholesterol 7 alpha hydroxylase , gene knockdown , abca1 , long non coding rna , biology , transcription factor , microbiology and biotechnology , metabolism , cholesterol , rna interference , transcription (linguistics) , lipid metabolism , activator (genetics) , rna , endocrinology , medicine , biochemistry , gene , transporter , linguistics , philosophy
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)