CircFOXP1 alleviates brain injury after acute ischemic stroke by regulating STAT3/apoptotic signaling.
Transl Res
; 257: 15-29, 2023 07.
Article
em En
| MEDLINE
| ID: mdl-36787831
ABSTRACT
According to previous studies, circular RNAs (circRNAs) are involved in multiple pathological processes of acute ischemic stroke (AIS). However, the relationship between circFOXP1 and IS has not yet been reported. Here, we found that circFOXP1 expression was significantly decreased in the peripheral blood of AIS patients compared to controls and was associated with the severity and prognosis of AIS. Functionally, knockdown and overexpression of circFOXP1 promoted and inhibited apoptotic signaling, respectively, following oxygen-glucose deprivation/reperfusion (OGD/R) treatment in vitro. Adeno-associated virus (AAV)-mediated circFOXP1 overexpression attenuated neurological deficits and improved functional recovery after transient middle cerebral artery occlusion (tMCAO) treatment in vivo. Mechanistically, decreased QKI expression inhibited circFOXP1 biogenesis under hypoxic conditions. Decreased circFOXP1 expression accelerated signal transducer and activator of transcription 3 (STAT3) protein degradation by binding to and increasing STAT3 protein ubiquitination, ultimately aggravating brain injury after cerebral ischemia by activating apoptotic signaling. In summary, our study is the first to reveal that circFOXP1 alleviates brain injury after cerebral ischemia by regulating STAT3/apoptotic signaling, which provides a potentially novel therapeutic target for AIS.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lesões Encefálicas
/
Traumatismo por Reperfusão
/
Isquemia Encefálica
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Acidente Vascular Cerebral
/
AVC Isquêmico
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Transl Res
Ano de publicação:
2023
Tipo de documento:
Article