Construction of a circular RNA-based competing endogenous RNA network to screen biomarkers related to intervertebral disc degeneration

Yu, Bin; Zhu, Zhaojin; Hu, Tao; Lu, Jiawei; Shen, Beiduo; Wu, Tongde; Guo, Kai; Chaudhary, Surendra Kumar; Feng, Hao; Zhao, Weidong; Wu, Desheng

doi:10.1186/s12891-022-05579-0

Cited by 2 publications

(2 citation statements)

References 59 publications

(55 reference statements)

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“…However, unlike this study, the mRNA data was not integrated. Similarly, other studies constructed ceRNA research networks using GEO databases, but the circRNA, mRNA, and miRNA databases chosen in this study differed from those utilized in the aforementioned studies 13 , 35 , 36 . Future research could summarize these studies to obtain more precise potential regulatory sites.…”

Section: Discussionmentioning

confidence: 99%

CircEYA3 aggravates intervertebral disc degeneration through the miR-196a-5p/EBF1 axis and NF-κB signaling

Wang,

Yan,

Song

et al. 2024

Commun Biol

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Intervertebral disc degeneration (IDD) is a well-established cause of disability, and extensive evidence has identified the important role played by regulatory noncoding RNAs, specifically circular RNAs (circRNAs) and microRNAs (miRNAs), in the progression of IDD. To elucidate the molecular mechanism underlying IDD, we established a circRNA/miRNA/mRNA network in IDD through standardized analyses of all expression matrices. Our studies confirmed the differential expression of the transcription factors early B-cell factor 1 (EBF1), circEYA3, and miR-196a-5p in the nucleus pulposus (NP) tissues of controls and IDD patients. Cell proliferation, apoptosis, and extracellular mechanisms of degradation in NP cells (NPC) are mediated by circEYA3. MiR-196a-5p is a direct target of circEYA3 and EBF1. Functional analysis showed that miR-196a-5p reversed the effects of circEYA3 and EBF1 on ECM degradation, apoptosis, and proliferation in NPCs. EBF1 regulates the nuclear factor kappa beta (NF-кB) signalling pathway by activating the IKKβ promoter region. This study demonstrates that circEYA3 plays an important role in exacerbating the progression of IDD by modulating the NF-κB signalling pathway through regulation of the miR196a-5p/EBF1 axis. Consequently, a novel molecular mechanism underlying IDD development was elucidated, thereby identifying a potential therapeutic target for future exploration.

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Section: Discussionmentioning

confidence: 99%

CircEYA3 aggravates intervertebral disc degeneration through the miR-196a-5p/EBF1 axis and NF-κB signaling

Wang,

Yan,

Song

et al. 2024

Commun Biol

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“…Recent studies have revealed that endogenous non-coding RNAs (ncRNAs), including circular RNAs (circRNAs) and microRNAs (miRNAs), participate in numerous biological and pathological processes. [12][13][14][15][16] Signi cantly, circRNAs have a complete circular structure with the characteristics of stabilization and biological functional diversity. Several studies have indicated that circRNAs act as sponges for miRNAs and speci cally bind to them.…”

Section: Introductionmentioning

confidence: 99%

CircEYA3 aggravates intervertebral disc degeneration through miR-196a-5p/EBF1 axis and NF-κB signaling pathway

Wang

Song

et al. 2023

Preprint

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Background Intervertebral disc degeneration (IDD) is one of the most frequent causes of disability. Currently, there is an incomplete understanding of the molecular mechanism that underlies the pathogenesis and progression of IDD..Regulatory non-coding RNAs, including circular RNAs (circRNAs) and microRNAs (miRNAs) play an important role in IDD progression. This study aimed to examine the role and molecular mechanism of circEYA3 in IDD.Methods In order to gain a deeper understanding of the potential regulatory effects of circRNAs, miRNAs, and mRNAs in IDD, all expression matrices underwent standardized analyses. The involvement of the circEYA3/miR-196a-5p/EBF1 axis in IDD was confirmed through both in vivo and in vitro experiments. The molecular mechanism of EBF1 in IDD was further elucidated through various methods, including Chip-seq analysis and Immunofluorescence staining.Results Firstly, a circRNA/miRNA/mRNA network in IDD was constructed according to the standardized analyses of all expression matrixes. We identified differential expression of transcription factor EBF1, circEYA3 and microRNA-196a-5p in normal and IDD NP tissues. Alteration of circEYA3 mediated the degradation of extracellular mechanisms (ECM), apoptosis and proliferation of NP cells (NPC). MiR-196a-5p was identified as a direct regulatory target of circEYA3 and EBF1. Functional analysis showed that circEYA3 and EBF1 modulated ECM degradation, apoptosis and proliferation of NPC, which could be reversed by miR-196a-5p. EBF1 regulated the activity of the NF-кB signaling pathway by activating the promoter region of IKKβ. Collectively, The circEYA3 modulated the progression of IDD and mediated the activity of the NF-kB signaling pathway by regulating the miR196a-5p/EBF1 axis.Conclusions Our research proposed a new molecular mechanism for the development of IDD and provided a prospective therapeutic target for IDD.

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Construction of a circular RNA-based competing endogenous RNA network to screen biomarkers related to intervertebral disc degeneration

Cited by 2 publications

References 59 publications

CircEYA3 aggravates intervertebral disc degeneration through the miR-196a-5p/EBF1 axis and NF-κB signaling

CircEYA3 aggravates intervertebral disc degeneration through the miR-196a-5p/EBF1 axis and NF-κB signaling

CircEYA3 aggravates intervertebral disc degeneration through miR-196a-5p/EBF1 axis and NF-κB signaling pathway

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