Circular RNA expression profile and potential function of hsa_circRNA_101238 in human thoracic aortic dissection

// Meisheng Zou 1,2,* , Chixiong Huang 1,* , Xinzhong Li 1 , Xiang He 1 , Yanmei Chen 1 , Wangjun Liao 3 , Yulin Liao 1 , Jie Sun 1,4 , Ze Liu 2 , Lintao Zhong 1 and Jianping Bin 1 1 Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China 2 Wards of Cadres, Guangzhou General Hospital of Guangzhou Military Region, Guangzhou, China 3 Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China 4 Department of Cardiology, Zhongshan Hospital, Sun Yat-Sen University, Zhongshan, China * These authors have contributed equally to this work Correspondence to: Jianping Bin, email: // Lintao Zhong, email: // Keywords : thoracic aortic dissection, circular RNA, microarray, biomathematics, Pathology Section Received : February 12, 2017 Accepted : June 18, 2017 Published : July 05, 2017 Abstract Objective: To assess the circular RNAs (circRNAs) expression profile and explore the potential functions in human thoracic aortic dissection (TAD). Methods: The differentially expressed circRNAs profiles of the aortic segments between human type A TAD patients ( n =3) and age-matched normal donors (NA; n =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. Results: 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. Conclusions: 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.