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J Stroke Cerebrovasc Dis ; 33(4): 107613, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38301749

RESUMO

OBJECTIVES: Previous studies have identified abnormal expression of lncRNA SNHG12 in ischemic stroke, but the underlying molecular mechanism remains unclear. MATERIALS AND METHODS: Through database predictions, m6A methylation sites were found on SNHG12, suggesting post-transcriptional modification. To further elucidate the role of SNHG12 and m6A methyltransferase WTAP in oxygen-glucose deprivation/reperfusion (OGD/R)-induced damage in cerebral microvascular endothelial cells, we conducted investigations. Additionally, we examined the impact of m6A methyltransferase WTAP on SNHG12 expression. RESULTS: Overexpressing SNHG12 in bEnd.3 cells was found to inhibit cell proliferation and promote apoptosis, as well as activate the production of reactive oxygen species and inflammatory cytokines (E-selectin, IL-6 and MCP-1), along with angiogenic proteins (VEGFA and FGFb). Conversely, SNHG12 knockdown alleviated OGD/R-induced damage to BEnd.3 cells, resulting in improved cell proliferation, reduced apoptosis, decreased ROS and LDH production, as well as diminished expression of inflammatory cytokines (E-selectin, IL-6 and MCP-1) and angiogenic proteins (VEGFA and FGFb). Furthermore, WTAP was found to positively regulate SNHG12 expression, and WTAP knockdown in bEnd.3 cells under the OGD/R conditions inhibited cell proliferation, promoted apoptosis, and increased ROS and LDH production. CONCLUSION: These findings suggest that WTAP may play a crucial role in SNHG12-mediated OGD/R-induced damage in bEnd.3 cells. More molecular experiments are needed to further analyze its mechanism. Overall, our study helps to enrich our understanding of the dysregulation of SNHG12 in ischemic stroke.


Assuntos
Proteínas de Ciclo Celular , AVC Isquêmico , RNA Longo não Codificante , Traumatismo por Reperfusão , Animais , Humanos , Camundongos , Oxigênio/metabolismo , Células Endoteliais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Selectina E , Glucose , Interleucina-6/metabolismo , AVC Isquêmico/metabolismo , Reperfusão , Proteínas Angiogênicas/metabolismo , Metiltransferases/metabolismo , Traumatismo por Reperfusão/metabolismo , Apoptose , Fatores de Processamento de RNA/metabolismo
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