Long Noncoding RNA HOXC-AS1 Suppresses Ox-LDL-Induced Cholesterol Accumulation Through Promoting HOXC6 Expression in THP-1 Macrophages

Long Noncoding RNA HOXC-AS1 Suppresses Ox-LDL-Induced Cholesterol Accumulation Through Promoting HOXC6 Expression in THP-1 Macrophages
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长非编码 RNA HOXC-AS1 通过促进 THP-1 巨噬细胞中 HOXC6 的表达来抑制 Ox-LDL 诱导的胆固醇积累

DOI:
10.1089/dna.2016.3422
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发表时间:
2016-11-01
影响因子:
3.1
通讯作者:
Wang, Qian
Wang, Qian
中科院分区:
生物学4区
文献类型:
--
作者:
Huang, Chuan;Hu, Yan-Wei;Wang, Qian

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动脉粥样硬化是心血管疾病的共同病理基础,心血管疾病仍然是导致死亡的主要原因。长链非编码RNA(longnoncodingRNAs,lncRNAs)是近年来研究较多的参与基因调控的非蛋白质编码RNA,但其在动脉粥样硬化中的调控机制尚不清楚。在这项研究中,我们发现lncRNA HOXC簇反义RNA 1(HOXC-AS 1)和同源框C6(HOXC 6)在颈动脉粥样硬化中表达下调。结果证实,在动脉粥样硬化斑块和正常动脉内膜组织的定量逆转录PCR和蛋白质印迹分析。慢病毒介导的HOXC-AS 1过表达诱导THP-1巨噬细胞HOXC 6在mRNA和蛋白水平的表达。氧化型低密度脂蛋白(Ox-LDL)可抑制HOXC-AS 1和HOXC-6的表达,且呈时间依赖性。过表达HOXC-AS 1可部分抑制Ox-LDL诱导的胆固醇蓄积。
Atherosclerosis is a common pathological basis of cardiovascular disease, which remains the leading cause of mortality. Long noncoding RNAs (lncRNAs) are newly studied non-protein-coding RNAs involved in gene regulation, but how lncRNAs exert regulatory effect on atherosclerosis remains unclear. In this study, we found that lncRNA HOXC cluster antisense RNA 1 (HOXC-AS1) and homeobox C6 (HOXC6) were downregulated in carotid atherosclerosis by performing microarray analysis. The results were verified in atherosclerotic plaques and normal arterial intima tissues by quantitative reverse transcription PCR and western blot analysis. Lentivirus-mediated overexpression of HOXC-AS1 induced HOXC6 expression at mRNA and protein levels in THP-1 macrophages. Besides, oxidized low-density lipoprotein (Ox-LDL) decreased expression of HOXC-AS1 and HOXC6 in a time-dependent manner. Induction of cholesterol accumulation by Ox-LDL could be partly suppressed by overexpression of HOXC-AS1.