Competitive binding of circCCDC6 to microRNA-128-3p activates TXNIP/NLRP3 pathway and promotes cerebral ischemia-reperfusion defects

  • ChongShu Wang Department of Neurology, The Fourth People’s Hospital of Shenyang, Shenyang City, Liaoning Province, 110001, China
  • MingMing Dong Department of Neurology, The Fourth People’s Hospital of Shenyang, Shenyang City, Liaoning Province, 110031, China
  • XiaoYi Zhang Department of Geriatric Medicine, The First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, 110001, China
  • XiaoYu Wang Department of Neurology, Liaoyang Central Hospital, Liaoyang City, Liaoning Province, 111010, China
  • Yan Zhao Department of Neurology, The Fourth People’s Hospital of Shenyang, Shenyang City, Liaoning Province, 110031, China
  • Yunpeng Cao Department of Neurology, The Fourth People’s Hospital of Shenyang, Shenyang City, Liaoning Province, 110001, China
DOI: https://doi.org/10.18388/abp.2020_6552

Abstract

Objective: Circular RNAs (circRNAs) are enriched in the brain and involved in various central nervous system diseases. The potential role of circCCDC6 in cerebral ischemia-reperfusion defects was partly elucidated in the work. Methods: A middle cerebral artery occlusion/reperfusion (MCAO/R) rat model and an oxygen-glucose deprivation and re-oxygenation (OGD/R)-treated SH-SY5Y cell model were constructed. CircCCDC6 expression in the two models was examined, and circCCDC6-involved mechanisms in neuronal pyroptosis and inflammation were analyzed through loss- and gain-of-function assays. Results: MCAO/R rat brain tissues and OGD/R-treated SH-SY5Y cells exhibited upregulated circCCDC6. Silencing circCCDC6 attenuated neuronal pyroptosis and inflammation in the brain tissue of MCAO/R rats. Overexpressing circCCDC6 or inhibiting miR-128-3p stimulated OGD/R-induced pyroptosis and inflammation in SH-SY5Y cells, while upregulating miR-128-3p attenuated OGD/R injury. CircCCDC6 silencing-induced effects on SH-SY5Y cells were antagonized by TXNIP overexpression. Conclusion: Mechanistically, circCCDC6 mediates miR-128-3p and activates TXNIP/NLRP3, thereby promoting OGD/R-induced neuronal pyroptosis and inflammation. CircCCDC6 may provide a new strategy for the treatment of MCAO/R.

Published
2023-11-07
Issue
Vol. 70 No. 4 (2023)
Section
Articles

Copyright (c) 2023 ChongShu Wang, MingMing Dong, XiaoYi Zhang, XiaoYu Wang, Yan Zhao, Yunpeng Cao

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