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- Title
Hsa_circ_0031608: A Potential Modulator of VSMC Phenotype in the Rupture of Intracranial Aneurysms.
- Authors
Wang, Chuanchuan; Luo, Yin; Tang, Haishuang; Yan, Yazhou; Chang, Xiaozan; Zhao, Rui; Li, Qiang; Yang, Pengfei; Hong, Bo; Xu, Yi; Huang, Qinghai; Liu, Jianmin
- Abstract
Background and Purpose: Phenotypic modulation of vascular smooth muscle cells (VSMCs) plays an important role in the development of intracranial aneurysms (IAs). Growing evidence has demonstrated that circular RNAs (circRNAs) may serve as a potential modulator of VSMC phenotype in various vascular diseases. This study aimed to assess the potential function of circRNAs in the rupture of IAs and VSMC phenotypic modulation. Methods: Using surgically dissected human ruptured (n = 8) and unruptured (n = 8) IA lesions, differentially expressed circRNAs were screened by transcriptomic sequencing and verified using qRT-PCR. Based on the screened circRNA, we predicted and screened the combined miRNA and downstream mRNAs to construct circRNA-miRNA-mRNA networks. Further in vitro experiments were performed to investigate the relationship between the validated circRNA and the phenotypic switching of VSMCs. Results: We found 1,373 differentially expressed genes in ruptured versus unruptured aneurysms. The top five dysregulated circRNAs were selected for qRT-PCR validation. We found hsa_circ_0031608 was both highly expressed in ruptured IAs and pro-inflammatory transformation of VSMCs. Then, a regulatory circRNA-miRNA-mRNA with one circRNA node, six miRNA nodes, and 84 mRNA nodes was constructed. GO analysis and KEGG pathway enrichment analysis were performed on mRNAs in the network. Then, a PPI network was built based on these mRNAs and five hub genes were identified (FOXO3, DICER1, CCND2, IGF1R, and TNRC6B) by the cytoHubba plugin in Cytoscape software. In vitro , overexpression of hsa_circ_0031608 influenced the expression of VSMC phenotypic markers validated by qPCR and Western blotting. Furthermore, hsa_circ_0031608 promoted the migration and proliferation capacity of VSMCs. Conclusion: hsa_circ_0031608 regulated the phenotypic modulation of VSMCs and played an important role in the rupture of IAs. The specific mechanism should be further studied and confirmed.
- Subjects
INTRACRANIAL aneurysm ruptures; PHENOTYPIC plasticity; CIRCULAR RNA; INTRACRANIAL aneurysms; VASCULAR smooth muscle; PHENOTYPES
- Publication
Frontiers in Molecular Neuroscience, 2022, Vol 15, p1
- ISSN
1662-5099
- Publication type
Article
- DOI
10.3389/fnmol.2022.842865