Yang Yao Guo, Li Mei Xia, Kou Lei, Zhou You, Qin Yan Wen, Liu Xiao Jun, Chen Zhong
The Department of Vascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Biomed Environ Sci. 2016 Oct;29(10):713-723. doi: 10.3967/bes2016.096.
This study is aimed at observing the role of long noncoding RNAs (lncRNAs) in the pathogenesis of abdominal aortic aneurysm (AAA).
LncRNA and mRNA expression signatures of AAA tissues and normal abdominal aortic tissues (NT) were analyzed by microarray and further verified by Real-time quantitative reverse-transcription PCR (qRT-PCR). The lncRNAs-mRNAs targeting relationships were identified using computational analysis. The effect of lnc-ARG on 5-lipoxygenase (ALOX5) expression was tested in HeLa cells.
Differential expressions of 3,688 lncRNAs and 3,007 mRNAs were identified between AAA and NT tissues. Moreover, 1,284 differentially expressed long intergenic noncoding RNAs and 206 differentially expressed enhancer-like lncRNAs adjacent to protein-coding genes were discerned by bioinformatics analysis. Some differentially expressed lncRNAs and mRNAs between AAA and normal tissue samples were further verified using qRT-PCR. A co-expression network of coding and noncoding genes was constructed based on the correlation analysis between the differentially expressed lncRNAs and mRNAs. In addition, the lnc-ARG located within the upstream of ALOX5 was sorted as a noncoding transcript by analyzing the protein-coding potential using computational analysis. Furthermore, we found that lnc-ARG can decrease the mRNA level of ALOX5 and reactive oxygen species production in HeLa cells.
This study revealed new lncRNA candidates are related to the pathogenesis of AAA.
本研究旨在观察长链非编码RNA（lncRNA）在腹主动脉瘤（AAA）发病机制中的作用。
通过微阵列分析AAA组织和正常腹主动脉组织（NT）的lncRNA和mRNA表达特征，并通过实时定量逆转录PCR（qRT-PCR）进一步验证。使用计算分析确定lncRNAs与mRNAs的靶向关系。在HeLa细胞中检测lnc-ARG对5-脂氧合酶（ALOX5）表达的影响。
在AAA组织和NT组织之间鉴定出3688个lncRNAs和3007个mRNAs的差异表达。此外，通过生物信息学分析识别出1284个差异表达的长链基因间非编码RNA和206个与蛋白质编码基因相邻的差异表达的增强子样lncRNAs。使用qRT-PCR进一步验证了AAA组织和正常组织样本之间一些差异表达的lncRNAs和mRNAs。基于差异表达的lncRNAs和mRNAs之间的相关性分析构建了编码和非编码基因的共表达网络。此外，通过计算分析蛋白质编码潜力，将位于ALOX5上游的lnc-ARG分类为非编码转录本。此外，我们发现lnc-ARG可以降低HeLa细胞中ALOX5的mRNA水平和活性氧的产生。
本研究揭示了与AAA发病机制相关的新的lncRNA候选物。
