Impact of high fat diet on long non-coding RNAs and messenger RNAs expression in the aortas of ApoE(-/-) mice.

Impact of high fat diet on long non-coding RNAs and messenger RNAs expression in the aortas of ApoE(-/-) mice.
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高脂饮食对ApoE(-/-)小鼠主动脉长链非编码RNA和信使RNA表达的影响

DOI:
10.1038/srep34161
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发表时间:
2016-10-04
期刊:
影响因子:
4.6
通讯作者:
Li JM
Li JM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bao MH;Luo HQ;Chen LH;Tang L;Ma KF;Xiang J;Dong LP;Zeng J;Li GY;Li JM

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动脉粥样硬化是一种慢性多因素炎症性疾病,在全球范围内高发,已成为人类死亡的主要原因。本研究旨在通过检测lncRNAs和mRNAs的全基因组表达谱来研究高脂饮食对载脂蛋白E(−/−)小鼠动脉粥样硬化的影响。共鉴定出354个差异表达的≥(LncRNA2.0倍)。同时,从同一芯片中发现了357个差异表达的mRNAs。在qPCR和微阵列检测中,lncRNAs和mRNAs的表达差异是一致的。对与lncRNAs相关的mRNAs的注释结果表明,与之相关的共同途径是代谢和炎症。超几何分布分析表明,差异表达的lncRNAs主要受Myod1、RXRA、PPARG、Tcf3等转录因子的调控,另外对前20个差异表达的lncRNAs进行了LncRNA-靶标-转录因子网络分析。结果表明,HNF4a、Ppara、VDR和Runx3是最有可能调节这些lncRNAs产生的转录因子,可能在动脉粥样硬化的炎症和代谢过程中发挥作用。简而言之,本研究确定了一组失调的lncRNAs和mRNAs,它们可能是与高脂饮食相关的动脉粥样硬化相关的潜在生物标志物或药物靶点。
Atherosclerosis is a chronic multifactorial inflammatory disease with high prevalence worldwide, and has become the leading cause of death. The present study was designed to investigate the impact of high-fat diet on ApoE(−/−) mice exhibiting atherosclerosis by detecting the genome-wide expression profile of lncRNAs and mRNAs. A total of 354 differentially expressed lncRNAs were identified (≥2.0 folds). Simultaneously, 357 differentially expressed mRNAs from the same chip were found. The expression differences of lncRNAs and mRNAs were consistent in both qPCR and microarray detection. Annotation results of the mRNAs which correlated with lncRNAs showed that the commonly related pathways were metabolism and inflammation. Hypergeometric distribution analysis indicated that the differentially expressed lncRNAs had been mostly regulated by transcription factors (TFs) such as Myod1, Rxra, Pparg, Tcf3, etc. Additional lncRNA-target-TFs network analysis was conducted for the top 20 differentially expressed lncRNAs. The results indicated Hnf4a, Ppara, Vdr, and Runx3 as the TFs most likely to regulate the production of these lncRNAs, and might play roles in inflammatory and metabolic processes in atherosclerosis. In a nutshell, the present study identified a panel of dysregulated lncRNAs and mRNAs that may be potential biomarkers or drug targets relevant to the high-fat diet related atherogenesis.
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