Inhibition of long noncoding RNA growth arrest–specific 5 attenuates cerebral injury induced by deep hypothermic circulatory arrest in rats

Gao, Shilun; Gu, Tingting; Shi, Enyi; Tang, Rui; Liu, Jinduo; Shi, Jiang

doi:10.1016/j.jtcvs.2019.01.050

Cited by 5 publications

(8 citation statements)

References 32 publications

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“…15,21,22 Gu et al reported that lncRNA-GAS5 could competitively inhibit the expression of miR-23a, providing a strong cerebral protective effect through modulating the PTEN pathway. 19 In vitro studies using oxygen and glucose-deprived primary neuron cultures under hypothermia showed a downregulation of ischemia tolerance-related protein SUMO2 mediated by miR-194-5p. 9 In our study, miR-194-5p was predicted to be…”

Section: Discussionmentioning

confidence: 99%

Differential expression profiles of circular RNAs in the rat hippocampus after deep hypothermic circulatory arrest

Liu

Zhang

et al. 2021

Artificial Organs

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Neurological dysfunction commonly occurs after cardiac surgery with deep hypothermic circulatory arrest (DHCA). The mechanisms underlying DHCA-associated brain injury remain poorly understood. This study determined the changes in expression profiles of circular RNAs (circRNAs) in the hippocampus in rats that underwent DHCA, with an attempt to explore the potential role of circRNAs in the brain injury associated with DHCA. Adult male Sprague Dawley rats were subjected to cardiopulmonary bypass with DHCA. Brain injury was evaluated by neurological severity scores and histological as well as transmission electron microscope examinations. The expression profiles of circRNAs in the hippocampal tissues were screened by microarray. Quantitative real-time PCR (RT-qPCR) was used to validate the reliability of the microarray results. Bioinformatic algorithms were applied to construct a competing endogenous RNA (ceRNA) network, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore the potential biological roles of the circRNAs. Out of 14 145 circRNAs screened, 56 were differentially expressed in the hippocampus between the DHCA and sham-operated rats, including 30 upregulated and 26 downregulated circRNAs. The expression changes of six selected circRNAs (upregulated: rno_cir-cRNA_011190, rno_circRNA_012988, rno_circRNA_000544; downregulated: rno_circRNA_010393, rno_circRNA_012043, rno_circRNA_015149) were further confirmed by RT-qPCR. Bioinformatics analysis showed the enrichment of these confirmed circRNAs and their potential target mRNAs in several KEGG pathways including histidine metabolism, adipocytokine signaling, and cAMP signaling. By revealing the change expression profiles of circRNAs in the brain after DHCA, this study indicates possible involvements of these dysregulated circRNAs in brain injury and suggests a potential of targeting circRNAs for prevention and treatment of neurological dysfunction associated with DHCA.

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Section: Discussionmentioning

confidence: 99%

Differential expression profiles of circular RNAs in the rat hippocampus after deep hypothermic circulatory arrest

Liu

Zhang

et al. 2021

Artificial Organs

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“…Although the mortality and morbidity after cardiovascular surgeries have been substantially improved, the utilization of DHCA can cause damage to multiple systems, including but not limited to the cardiovascular, kidney, and nervous systems (Cooper et al, 2000;Algra et al, 2014;Bartels et al, 2014;Fang et al, 2019). Stroke and temporary neurologic deficit were observed in 2 and 5.1% of patients undergoing aortic arch surgery using DHCA, respectively (Shi et al, 2020). The safe time range of DHCA is 20-30 min, and with the extension of DHCA time, the incidence of transient or persistent neurological dysfunction after DHCA surgery will significantly increase (Wei et al, 2015;Weber et al, 2019;Shi et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Stroke and temporary neurologic deficit were observed in 2 and 5.1% of patients undergoing aortic arch surgery using DHCA, respectively (Shi et al, 2020). The safe time range of DHCA is 20-30 min, and with the extension of DHCA time, the incidence of transient or persistent neurological dysfunction after DHCA surgery will significantly increase (Wei et al, 2015;Weber et al, 2019;Shi et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Identifying lncRNA- and Transcription Factor-Associated Regulatory Networks in the Cortex of Rats With Deep Hypothermic Circulatory Arrest

et al. 2021

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Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are involved in the mechanism underlying cerebral dysfunction after deep hypothermic circulatory arrest (DHCA), although the exact details have not been elucidated. To explore the expression profiles of lncRNAs and miRNAs in DHCA cerebral injury, we determined the lncRNA, miRNA and mRNA expression profiles in the cerebral cortex of DHCA and sham rats. First, a rat model of DHCA was established, and high-throughput sequencing was performed to analyze the differentially expressed RNAs (DERNAs). Then, the principal functions of the significantly deregulated genes were identified using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Expression networks (lncRNAs-miRNAs-mRNAs and transcription factors (TFs)-miRNAs-mRNAs) were also established. Finally, the expression of DERNAs was confirmed by quantitative real-time PCR (RT-qPCR). We identified 89 lncRNAs, 45 miRNAs and 59 mRNAs between the DHCA and sham groups and constructed a comprehensive competitive endogenous RNAs (ceRNAs) network. A TF-miRNA-mRNA regulatory network was also established. Finally, we predicted that Lcorl-miR-200a-3p-Ttr, BRD4-Ccl2 and Ep300-miR-200b-3p-Tmem72 may participate in the pathogenesis of DHCA cerebral injury.

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“…In their article in this edition of the Journal, Gao and coworkers 1 have demonstrated that inhibition of long noncoding RNA (lncRNA) growth arrest specific 5 (GAS5) expression attenuates cerebral injury in a rodent model of deep hypothermic circulatory arrest (DHCA). This protection, which was mediated through the microRNA-23a (miR-23a)/phosphatase and tensin homolog (PTEN) pathway, resulted in an increased expression of miR-23a, a decreased incidence of apoptosis in the hippocampus, and improved spatial learning and memory function.…”

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confidence: 99%

Commentary: Inhibition of gene expression—A novel strategy for cerebral protection during deep hypothermic circulatory arrest

Lazar

2020

The Journal of Thoracic and Cardiovascular Surgery

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In their article in this edition of the Journal, Gao and coworkers 1 have demonstrated that inhibition of long noncoding RNA (lncRNA) growth arrest specific 5 (GAS5) expression attenuates cerebral injury in a rodent model of deep hypothermic circulatory arrest (DHCA). This protection, which was mediated through the microRNA-23a (miR-23a)/phosphatase and tensin homolog (PTEN) pathway, resulted in an increased expression of miR-23a, a decreased incidence of apoptosis in the hippocampus, and improved spatial learning and memory function. Gao and coworkers 1 have provided new insight into the mechanisms for cerebral injury during DHCA and how such injury may alter learning and memory function. Nevertheless, there are several limitations with this study.As noted by Gao and coworkers, 1 a rodent DHCA model may not replicate the cerebral changes seen in human patients undergoing DHCA. Furthermore, it is unclear whether the changes in neuronal cell apoptosis that were produced in their rodent model will produce similar, if any neurologic deficits in humans. Transfection of the adenovirus-associated vector of GAS5 required 14 days, and the vector was administered by way of intraventricular injection. Such a time-consuming technique would not be applicable for patients undergoing aortic surgery requiring DHCA on an urgent or emergency basis. Furthermore, the need for an intracerebral injection increases the risk of additional morbidity in an already high-risk group of patients. Finally, because GAS5 has been shown to inhibit cell proliferation and promote apoptosis in gliomas, 2 the inhibition of GAS5 in humans has the potential to increase their susceptibility to malignant cerebral tumors.Gao and coworkers 1 are to be congratulated on performing an elegant set of experiments in a rodent model to demonstrate the potential of lncRNA GAS5 inhibition as a novel mechanism for cerebral protection during DHCA. Further studies will be necessary in a large animal model to demonstrate its potential applicability to human patients undergoing procedures involving DHCA. References 1. Gao S, Gu T, Shi E, Tang R, Liu J, Shi J. Inhibition of long noncoding RNA growth arrest-specific 5 attenuates cerebral injury induced by deep hypothermic circulatory arrest in rats. J Thorac Cardiovasc Surg. 2020;159:50-9. 2. Zhao X, Wang P, Liu J, Zheng J, Liu Y, Chen J, et al. GAS5 exerts tumorsuppressive function in human glioma cells by targeting miR-222. Mol Ther. 2015;23:1899-911.

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Inhibition of long noncoding RNA growth arrest–specific 5 attenuates cerebral injury induced by deep hypothermic circulatory arrest in rats

Cited by 5 publications

References 32 publications

Differential expression profiles of circular RNAs in the rat hippocampus after deep hypothermic circulatory arrest

Differential expression profiles of circular RNAs in the rat hippocampus after deep hypothermic circulatory arrest

Identifying lncRNA- and Transcription Factor-Associated Regulatory Networks in the Cortex of Rats With Deep Hypothermic Circulatory Arrest

Commentary: Inhibition of gene expression—A novel strategy for cerebral protection during deep hypothermic circulatory arrest

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