A circular RNA from NFIX facilitates oxidative stress-induced H9c2 cells apoptosis

Cui, Xianglun; Dong, Yanhan; Li, Mingyu; Wang, Xuekang; Jiang, Meiqing; Yang, Weiwei; Liu, Gege; Sun, Shuqi; Xu, Wu

doi:10.1007/s11626-020-00476-z

Cited by 12 publications

(29 citation statements)

References 51 publications

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“…In the skeletal muscle, Nfix can also regulate myogenesis [ 99 , 100 ], however, deletion of Nfix leads to decreased muscle regeneration and has been implicated in the pathogenesis of muscular dystrophies [ 101 ]. The knockdown of Nfix in a myoblast cell line was protective against oxidative stress [ 102 ], thus indicating that this transcription factor may have a versatile role in health and disease. In the context of retinal degeneration, the upregulation of Cyba and Nfix transcripts reinforces the hypothesis that oxidative stress takes place and accelerates RGC death in ONC models [ 103 ].…”

Section: Discussionmentioning

confidence: 99%

Retinal Genomic Fabric Remodeling after Optic Nerve Injury

Victorino

Marra

Iacobaş

et al. 2021

Genes

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Glaucoma is a multifactorial neurodegenerative disease, characterized by degeneration of the retinal ganglion cells (RGCs). There has been little progress in developing efficient strategies for neuroprotection in glaucoma. We profiled the retina transcriptome of Lister Hooded rats at 2 weeks after optic nerve crush (ONC) and analyzed the data from the genomic fabric paradigm (GFP) to bring additional insights into the molecular mechanisms of the retinal remodeling after induction of RGC degeneration. GFP considers three independent characteristics for the expression of each gene: level, variability, and correlation with each other gene. Thus, the 17,657 quantified genes in our study generated a total of 155,911,310 values to analyze. This represents 8830x more data per condition than a traditional transcriptomic analysis. ONC led to a 57% reduction in RGC numbers as detected by retrograde labeling with 1,1′-dioctadecyl-3,3,3,3′-tetramethylindocarbocyanine perchlorate (DiI). We observed a higher relative expression variability after ONC. Gene expression stability was used as a measure of transcription control and disclosed a robust reduction in the number of very stably expressed genes. Predicted protein–protein interaction (PPI) analysis with STRING revealed axon and neuron projection as mostly decreased processes, consistent with RGC degeneration. Conversely, immune response PPIs were found among upregulated genes. Enrichment analysis showed that complement cascade and Notch signaling pathway, as well as oxidative stress and kit receptor pathway were affected after ONC. To expand our studies of altered molecular pathways, we examined the pairwise coordination of gene expressions within each pathway and within the entire transcriptome using Pearson correlations. ONC increased the number of synergistically coordinated pairs of genes and the number of similar profiles mainly in complement cascade and Notch signaling pathway. This deep bioinformatic study provided novel insights beyond the regulation of individual gene expression and disclosed changes in the control of expression of complement cascade and Notch signaling functional pathways that may be relevant for both RGC degeneration and remodeling of the retinal tissue after ONC.

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Section: Discussionmentioning

confidence: 99%

Retinal Genomic Fabric Remodeling after Optic Nerve Injury

Victorino

Marra

Iacobaş

et al. 2021

Genes

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“…In the skeletal muscle, Nfix can also regulate myogenesis [107,108], however deletion of Nfix leads to decreased muscle regeneration and has been implicated in the pathogenesis of muscular dystrophies [109]. The knock-down of Nfix in a myoblast cell line was protective against oxidative stress [110], thus indicating that this transcription factor may have a versatile role in health and disease. In the context of retinal degeneration, the up-regulation of Cyba and Nfix transcripts reinforces the hypothesis that oxidative stress takes place and accelerates RGC death in ONC models [111].…”

Section: Discussionmentioning

confidence: 99%

Retinal Genomic Fabrics Remodeling after Optic Nerve Injury

Victorino¹,

Marra²,

Iacobaş³

et al. 2021

Preprint

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Glaucoma is a multifactorial neurodegenerative disease, characterized by degeneration of the retinal ganglion cells (RGCs). There has been little progress in developing efficient strategies for neuroprotection in glaucoma. We profiled the retina transcriptome of Lister Hooded rats at 2 weeks after optic nerve crush (ONC) and analyzed the data from the Genomic Fabric Paradigm (GFP) to bring additional insights into the molecular mechanisms of the retinal remodeling after induction of RGC degeneration. GFP considers for the expression of each gene 3 independent characteristics: level, variability and correlation with each other gene. Thus, the 17,657 quantified genes our study generated a total of 155,911,310 values to analyze. This represents 8,830x more data per condition than a traditional transcriptomic analysis. ONC led to a 57% reduction in RGC numbers as detected by retrograde labeling with DiI. We observed a higher Relative Expression Variability after ONC. Gene expression stability was used as a measure of transcription control and disclosed a robust reduction in the number of very stably expressed genes. Predicted Protein-Protein interaction (PPI) analysis with STRING revealed axon and neuron projection as mostly decreased processes, consistent with RGC degeneration. Conversely, immune response PPIs were found among up-regulated genes. Enrichment analysis showed that Complement Cascade and Notch Signaling Pathway, as well as Oxidative Stress and Kit Receptor Pathway were affected after ONC. To expand our studies of altered molecular pathways, we examined the pair-wise coordination of gene expressions within each pathway and within the entire transcriptome using Pearson correlations. ONC increased the number of synergistically coordinated pairs of genes and the number of similar profiles mainly in Complement Cascade and Notch Signaling Pathway. This deep bioinformatic study provides novel insights beyond the regulation of individual gene expression and discloses changes in the control of expression of Complement Cascade and Notch Signaling functional pathways that may be relevant for both RGC degeneration and remodeling of the retinal tissue after ONC.

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“…CircNFIX is abundant, conservative, and stable in H9c2 cells. In an anoxic environment, circNFIX expression was significantly downregulated in cardiomyocytes under oxidative stress [107]. Chen and colleagues found that the HG treatment can significantly increase ROS and MDA levels and decrease SOD activity and SOD2 expression.…”

Section: Circrnas Regulate Various Diseases Via Modulatingmentioning

confidence: 99%

Emerging Clues of Regulatory Roles of Circular RNAs through Modulating Oxidative Stress: Focus on Neurological and Vascular Diseases

Jiang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Circular RNAs (circRNAs) are novel noncoding RNAs that play regulatory roles in gene expression. Dysregulation of circRNAs is associated with the development and progression of several diseases, such as diabetes mellitus, nervous system diseases, cardiovascular diseases, and cancer. CircRNAs functionally participate in cell physiological activities through various molecular mechanisms. However, these molecular mechanisms are unclear. Oxidative stress is an essential factor in the pathogenesis of various diseases, including neurological diseases. Emerging roles of circRNAs have been identified in different systems in response to oxidative stress. In this review, we summarize the current understanding of circRNA biogenesis, properties, expression profiles, and the clues indicating the regulatory roles of circRNAs through oxidative stress in various systems, especially the nervous system.

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A circular RNA from NFIX facilitates oxidative stress-induced H9c2 cells apoptosis

Cited by 12 publications

References 51 publications

Retinal Genomic Fabric Remodeling after Optic Nerve Injury

Retinal Genomic Fabric Remodeling after Optic Nerve Injury

Retinal Genomic Fabrics Remodeling after Optic Nerve Injury

Emerging Clues of Regulatory Roles of Circular RNAs through Modulating Oxidative Stress: Focus on Neurological and Vascular Diseases

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