Zou Meisheng, Huang Chixiong, Li Xinzhong, He Xiang, Chen Yanmei, Liao Wangjun, Liao Yulin, Sun Jie, Liu Ze, Zhong Lintao, Bin Jianping
Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Wards of Cadres, Guangzhou General Hospital of Guangzhou Military Region, Guangzhou, China.
Oncotarget. 2017 Jul 5;8(47):81825-81837. doi: 10.18632/oncotarget.18998. eCollection 2017 Oct 10.
To assess the circular RNAs (circRNAs) expression profile and explore the potential functions in human thoracic aortic dissection (TAD).
The differentially expressed circRNAs profiles of the aortic segments between human type A TAD patients (=3) and age-matched normal donors (NA; =3) were analyzed using the Arraystar human circRNAs microarray. Quantitative real-time PCR was used to validate the expression pattern of circRNAs, parental genes, and hsa-miR-320a; Western blotting confirmed MMP9 expression with additional samples. Bioinformatic tools including network analysis, Gene ontology, and KEGG pathway analysis were utilized.
Among 8,173 detected circRNA genes, 156 upregulated and 106 downregulated significantly in human TAD as compared to NA (P£0.05). Quantitative real-time PCR showed an elevated expression of the upregulated hsa_circRNA_101238, hsa_circRNA_104634, hsa_circRNA_002271, hsa_circRNA_102771, hsa_circRNA_104349, COL1A1, and COL6A3 and reduced of the downregulated hsa_circRNA_102683, hsa_circRNA_005525, hsa_circRNA_103458, and FLNA. Gene ontology analysis revealed that the parental genes favored several pathological processes, such as negative regulation of cell proliferation and extracellular matrix organization. The circRNA-miRNA co-expression network predicted that 33 circRNAs might interact with at least one target miRNAs altered in TAD. KEGG pathway analysis revealed that 28 altered miRNAs were enriched on focal adhesion and vascular smooth muscle contraction. The hsa_circRNA_101238-miRNA-mRNA network indicated the highest degree of hsa-miR-320a. Quantitative real-time PCR and Western blot manifested the low expression of hsa-miR-320a and high of MMP9 in human TAD tissues, respectively.
This study revealed hundreds of differentially expressed circular RNAs in human TAD, suggesting that hsa_circRNA_101238 might inhibit the expression of hsa-miR-320a and increase that of MMP9 in TAD.
评估环状RNA（circRNAs）的表达谱，并探索其在人类胸主动脉夹层（TAD）中的潜在功能。
使用Arraystar人类circRNAs微阵列分析A型TAD患者（n = 3）与年龄匹配的正常供体（NA；n = 3）之间主动脉段差异表达的circRNAs谱。采用定量实时PCR验证circRNAs、亲本基因和hsa-miR-320a的表达模式；蛋白质免疫印迹法通过额外样本确认MMP9的表达。利用包括网络分析、基因本体论和KEGG通路分析在内的生物信息学工具。
在检测的8173个circRNA基因中，与NA相比，人类TAD中有156个显著上调，106个显著下调（P≤0.05）。定量实时PCR显示上调的hsa_circRNA_101238、hsa_circRNA_104634、hsa_circRNA_002271、hsa_circRNA_102771、hsa_circRNA_104349、COL1A1和COL6A3表达升高，而下调的hsa_circRNA_102683、hsa_circRNA_005525、hsa_circRNA_103458和FLNA表达降低。基因本体论分析显示，亲本基因参与了多个病理过程，如细胞增殖的负调控和细胞外基质组织。circRNA-miRNA共表达网络预测，33个circRNAs可能与TAD中至少一种改变的靶miRNA相互作用。KEGG通路分析显示，28个改变的miRNA在粘着斑和血管平滑肌收缩中富集。hsa_circRNA_101238-miRNA-mRNA网络显示hsa-miR-320a的连接度最高。定量实时PCR和蛋白质免疫印迹分别显示人类TAD组织中hsa-miR-320a表达低，MMP9表达高。
本研究揭示了人类TAD中数百个差异表达的环状RNA，提示hsa_circRNA_101238可能在TAD中抑制hsa-miR-320a的表达并增加MMP9的表达。
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