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Biochim Biophys Acta Mol Basis Dis ; 1870(6): 167278, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38834101

RESUMO

BACKGROUND: The dysfunction of human vascular smooth cells (hVSMCs) is significantly connected to the development of intracranial aneurysms (IAs). By suppressing the activity of microRNAs (miRNAs), circular RNAs (circRNAs) participate in IA pathogenesis. Nevertheless, the role of hsa_circ_0008571 in IAs remains unclear. METHODS: circRNA sequencing was used to identify circRNAs from human IA tissues. To determine the function of circ_0008571, Transwell, wound healing, and cell proliferation assays were conducted. To identify the target of circ_0008571, the analyses of CircInteractome and TargetScan, as well as the luciferase assay were carried out. Furthermore, circ_0008571 knockdown and over-expression were performed to investigate its functions in IA development and the underlying molecular mechanisms. RESULTS: Both hsa_circ_0008571 and Integrin beta 8 (ITGB8) were downregulated, while miR-145-5p transcription was elevated in the aneurysm wall of IAs patients compared to superficial temporal artery tissues. In vitro, cell migration and growth were dramatically suppressed after hsa_circ_0008571 overexpression. Mechanistically, has_circ_0008571 could suppress miR-145-5p activity by direct sponging. Moreover, we found that ITGB8 expression and the activation of the TGF-ß-mediated signaling pathway were significantly enhanced. CONCLUSION: The hsa_circ_0008571-miR-145-5p-ITGB8 axis plays an essential role in IA progression.


Assuntos
Proliferação de Células , Aneurisma Intracraniano , MicroRNAs , Músculo Liso Vascular , Miócitos de Músculo Liso , RNA Circular , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Aneurisma Intracraniano/genética , Aneurisma Intracraniano/patologia , Aneurisma Intracraniano/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Proliferação de Células/genética , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Movimento Celular/genética , Fenótipo , Masculino , Feminino , Pessoa de Meia-Idade , Células Cultivadas , Cadeias beta de Integrinas
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