Xi Lan1,2, Jidong Yan1,2, Juan Ren3, Bo Zhong4, Jing Li1,2, Yue Li1,2, Li Liu1,2, Jing Yi1,2, Qingzhu Sun1,2, Xudong Yang1,2, Jian Sun1,2, Liesu Meng1,2, Wenhua Zhu1,2, Rikard Holmdahl5, Dongmin Li1,2, Shemin Lu1,2. 1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China. 2. Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Beijing, China. 3. Department of Reproductive Medicine, the Fourth Hospital of Xi'an Jiaotong University, Xi'an, China. 4. Department of Pediatrics, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. 5. Division of Medical Inflammation Research, Department of Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Abstract
UNLABELLED: 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).
UNLABELLED: 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).