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.
Keywords
Abbreviations:
circRNA (circular RNA), AIS (acute ischemic stroke), OGD/R (oxygen-glucose deprivation/reperfusion), AAV (Adeno-associated virus), tMCAO (transient middle cerebral artery occlusion), DALYs (disability-adjusted life years), tPA (tissue plasminogen activator), SPF (specific pathogen-free), TTC (triphenyltetrazolium chloride), mNSS (modified neurological severity score), RPD (RNA pulldown), RIP (RNA immunoprecipitation), CLIP (crosslinking immunoprecipitation), Co-IP (coimmunoprecipitation), NIHSS (National Institute of Health stroke scale), mRS (modified Rankin Scale), CHX (cycloheximide)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: February 11, 2023
Accepted:
January 23,
2023
Received in revised form:
January 8,
2023
Received:
November 5,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Elsevier Inc. All rights reserved.
