验证主动脉夹层表达谱中的枢纽基因。
Verification of hub genes in the expression profile of aortic dissection.
机构信息
Department of Cardiovascular Surgery, Second Hospital of Jilin University, Changchun, Jilin, China.
Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo, Japan.
出版信息
PLoS One. 2019 Nov 21;14(11):e0224922. doi: 10.1371/journal.pone.0224922. eCollection 2019.
BACKGROUND
To assess the mRNA expression profile and explore the hub mRNAs and potential molecular mechanisms in the pathogenesis of human thoracic aortic dissection (TAD).
METHODOLOGY
mRNA microarray expression signatures of TAD tissues (n = 6) and non-TAD tissues (NT; n = 6) were analyzed by an Arraystar human mRNA microarray. Real-time PCR (qRT-PCR) was used to validate the results of the mRNA microarray. Bioinformatic tools, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, were utilized. Protein-protein interaction (PPI) networks were constructed based on data from the STRING database. Molecular Complex Detection (MCODE) and cytoHubba analyses were used to predict the strongest hub gene and pathway.
RESULTS
The top 10 hub genes were CDK1, CDC20, CCNB2, CCNB1, MAD2L1, AURKA, C3AR1, NCAPG, CXCL12 and ASPM, which were identified from the PPI network. Module analysis revealed that TAD was associated with the cell cycle, oocyte meiosis, the p53 signaling pathway, and progesterone-mediated oocyte maturation. The qRT-PCR results showed that the expression of all hub genes was significantly increased in TAD samples (p < 0.05). Immunostaining of Ki-67 and CDK1 showed a high proliferation state and high expression in TAD, respectively.
CONCLUSIONS
CDK1 could be used as a potential diagnostic biomarker and therapeutic target of TAD.
背景
评估人类胸主动脉夹层（TAD）发病机制中的 mRNA 表达谱，并探索关键 mRNA 和潜在的分子机制。
方法
通过 Arraystar 人类 mRNA 微阵列分析 TAD 组织（n=6）和非-TAD 组织（NT；n=6）的 mRNA 微阵列表达谱。实时 PCR（qRT-PCR）用于验证 mRNA 微阵列的结果。利用基因本体论和京都基因与基因组百科全书通路分析等生物信息学工具进行分析。基于 STRING 数据库中的数据构建蛋白质-蛋白质相互作用（PPI）网络。使用 Molecular Complex Detection（MCODE）和 cytoHubba 分析预测最强的关键基因和通路。
结果
从 PPI 网络中鉴定出前 10 个关键基因是 CDK1、CDC20、CCNB2、CCNB1、MAD2L1、AURKA、C3AR1、NCAPG、CXCL12 和 ASPM。模块分析表明，TAD 与细胞周期、卵母细胞减数分裂、p53 信号通路和孕激素介导的卵母细胞成熟有关。qRT-PCR 结果显示，所有关键基因在 TAD 样本中的表达均显著增加（p<0.05）。Ki-67 和 CDK1 的免疫染色分别显示 TAD 中存在高增殖状态和高表达。
结论
CDK1 可作为 TAD 的潜在诊断生物标志物和治疗靶点。
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