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

ABSTRACT: 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 (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.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.

SUBMITTER: Zou M

PROVIDER: S-EPMC5669851 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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

Zou Meisheng M Huang Chixiong C Li Xinzhong X He Xiang X Chen Yanmei Y Liao Wangjun W Liao Yulin Y Sun Jie J Liu Ze Z Zhong Lintao L Bin Jianping J

Oncotarget 20170705 47

<h4>Objective</h4>To assess the circular RNAs (circRNAs) expression profile and explore the potential functions in human thoracic aortic dissection (TAD).<h4>Methods</h4>The differentially expressed circRNAs profiles of the aortic segments between human type A TAD patients (<i>n</i>=3) and age-matched normal donors (NA; <i>n</i>=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 h ...[more]

PMID: 29137225

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Project description:Background: Circular RNAs (circRNAs), a novel class of endogenous noncoding RNAs, are involved in a variety of diseases, including several types of cancers. We hypothesized that circRNAs are involved in the tumorigenesis and development of clear cell renal cell carcinoma (ccRCC). Methods: To verify our hypothesis, we explored the circRNA expression profiles in 4 pairs of ccRCC tissues and their adjacent non-carcinoma tissues via microarray analysis. Selected circRNAs were further validated by qPCR. Moreover, hsa_circ_0005875 was selected for further study and the potential clinical values of hsa_circ_0005875 were investigated in 60 pairs of ccRCC tissues and adjacent normal controls. In addition, the role of hsa_circ_0005875 in ccRCC progression were performed using colony formation assay, Transwell assay and Martrigel-Transwell assay respectively. Finally, interactions between the circRNAs and miRNAs were predicted using Arraystar's miRNA target prediction software. Luciferase reporter assays were performed to evaluate the interaction between hsa_circ_0005875 and hsa_miR-145-5p. Results: The microarray data showed 1988 circRNAs were significantly dysregulated circRNAs, including 1033 upregulated and 955 downregulated ones in the ccRCC tissues. Hsa_circ_0005875 was confirmed to be significantly upregulated in the ccRCC tumor tissues and renal carcinoma cells. Further analysis revealed that hsa_circ_0005875 expression was associated with tumor size, pathological TNM stage, histological differentiation, and lymphatic metastasis. Functional experiments demonstrated that overexpression of hsa_circ_0005875 increased proliferation, migration and invasion abilities. Moreover, bioinformatics analysis and luciferase reporter assays suggest that hsa_circ_0005875 may serve as a ceRNA (competing endogenous RNA) of miR-145-5p to relieve the repressive effect of miR-145-5p on target ZEB2. Conclusions: These data indicate that hsa_circ_0005875 might play a role in promoting tumor growth and metastasis and be a potential biomarker of ccRCC.

Dataset Information

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

Publications

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

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