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

Abstract

Abstract 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.