2. Academic Validation
  3. CircAKT3 alleviates postoperative cognitive dysfunction by stabilizing the feedback cycle of miR-106a-5p/HDAC4/MEF2C axis in hippocampi of aged mice

CircAKT3 alleviates postoperative cognitive dysfunction by stabilizing the feedback cycle of miR-106a-5p/HDAC4/MEF2C axis in hippocampi of aged mice

  • Cell Mol Life Sci. 2024 Mar 13;81(1):138. doi: 10.1007/s00018-024-05156-9.
Xuan Wang 1,  Xiaole Tang 2,  Pengfei Zhu 1,  Dongyu Hua 1,  Zheng Xie 1,  Mingke Guo 1,  Mengxin Que 1,  Jing Yan 1,  Xing Li 1,  Qian Xia 1,  Xiaoxiao Luo 3,  Jiangjiang Bi 1,  Yilin Zhao 1,  Zhiqiang Zhou 1,  Shiyong Li 4,  Ailin Luo 5
Affiliations

Affiliations

  • 1 Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China.
  • 2 State Key Laboratory of Oncology in Southern China, Department of Anesthesiology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, China.
  • 3 Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 4 Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China. shiyongli@hust.edu.cn.
  • 5 Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China. alluo@hust.edu.cn.
PMID: 38478029 DOI: 10.1007/s00018-024-05156-9
Abstract

Circular RNAs (circRNAs) have garnered significant attention in the field of neurodegenerative diseases including Alzheimer's diseases due to their covalently closed loop structure. However, the involvement of circRNAs in postoperative cognitive dysfunction (POCD) is still largely unexplored. To identify the genes differentially expressed between non-POCD (NPOCD) and POCD mice, we conducted the whole transcriptome sequencing initially in this study. According to the expression profiles, we observed that circAKT3 was associated with hippocampal neuronal Apoptosis in POCD mice. Moreover, we found that circAKT3 overexpression reduced Apoptosis of hippocampal neurons and alleviated POCD. Subsequently, through bioinformatics analysis, our data showed that circAKT3 overexpression in vitro and in vivo elevated the abundance of miR-106a-5p significantly, resulting in a decrease of HDAC4 protein and an increase of MEF2C protein. Additionally, this effect of circAKT3 was blocked by miR-106a-5p inhibitor. Interestingly, MEF2C could activate the transcription of miR-106a-5p promoter and form a positive feedback loop. Therefore, our findings revealed more potential modulation ways between circRNA-miRNA and miRNA-mRNA, providing different directions and targets for preclinical studies of POCD.

Keywords

Perioperative neurocognitive disorders; Transcriptional regulation; circRNA; miRNA.

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