LncRNA CEBPA‐AS1 alleviates cerebral ischemia‐reperfusion injury by sponging miR‐340‐5p regulating APPL1/LKB1/AMPK pathway

• Published in: The FASEB journal 2022-01, Vol.36 (1), p.e22075-n/a
• Main Authors: Tu, Xiankun, Zhang, Huabin, Chen, Song, Ding, Yi‐hang, Wu, Xiyao, Liang, Risheng, Shi, Song‐sheng
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - biosynthesis; Adaptor Proteins, Signal Transducing - genetics; AMP-Activated Protein Kinase Kinases - biosynthesis; AMP-Activated Protein Kinase Kinases - genetics; AMP-Activated Protein Kinases - biosynthesis; AMP-Activated Protein Kinases - genetics; Animals; Apoptosis; APPL1/LKB1/AMPK pathway; CEBPA‐AS1; cerebral ischemia‐reperfusion injury; Cerebrovascular Disorders - genetics; Cerebrovascular Disorders - metabolism; Cerebrovascular Disorders - pathology; Disease Models, Animal; Gene Expression Regulation; MCAO/IR rat model; MicroRNAs - biosynthesis; MicroRNAs - genetics; miR‐340‐5p; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Rats; Rats, Sprague-Dawley; Reperfusion Injury - genetics; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; RNA, Long Noncoding - biosynthesis; RNA, Long Noncoding - genetics; Signal Transduction
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.202100826RR

Long non‐coding RNAs (lncRNAs) regulate neurological damage in cerebral ischemia‐reperfusion injury (CIRI). This study aimed to investigate the biological roles of lncRNA CEBPA‐AS1 in CIRI. Middle cerebral artery occlusion and ischemia‐reperfusion injury (MCAO/IR) rat model and oxygen‐glucose deprivation and reoxygenation (OGD/R) cell lines were generated; the expression of CEBPA‐AS1 was evaluated by qRT‐PCR. The effects of CEBPA‐AS1 on cell apoptosis and nerve damage were examined. The downstream microRNA (miRNA) and mRNA of CEBPA‐AS1 were predicted and verified. We found that overexpression of CEBPA‐AS1 could attenuate MCAO/IR‐induced nerve damage and neuronal apoptosis in the rat model. Knockdown of CEBPA‐AS1 aggravated cell apoptosis and enhanced the production of LDH and MDA in the OGD/R cells. Upon examining the molecular mechanisms, we found that CEBPA‐AS1 stimulated APPL1 expression by combining with miR‐340‐5p, thereby regulating the APPL1/LKB1/AMPK pathway. In the rescue experiments, CEBPA‐AS1 overexpression was found to attenuate OGD/R‐induced cell apoptosis and MCAO/IR induced nerve damage, while miR‐340‐5p reversed these effects of CEBPA‐AS1. In conclusion, CEBPA‐AS1 could decrease CIRI by sponging miR‐340‐5, regulating the APPL1/LKB1/AMPK pathway.