CircularRNA_104670 plays a critical role in intervertebral disc degeneration by functioning as a ceRNA

Abstract

This study was carried out to explore the roles of circular RNAs (circRNAs) in nucleus pulposus (NP) tissues in intervertebral disc degeneration (IDD). Differentially expressed circRNAs in IDD and normal NP tissues were identified based on the results of microarray analysis. Bioinformatics techniques were employed to predict the direct interactions of selected circRNAs, microRNAs (miR), and mRNAs. CircRNA_104670 was selected as the target circRNA due to its large multiplier expression in IDD tissues. After luciferase reporter and EGFP/RFP reporter assays, we confirmed that circRNA_104670 directly bound to miR-17-3p, while MMP-2 was the direct target of miR-17-3p. The receiver-operating characteristic (ROC) curve showed that circRNA_104670 and miR-17-3p had good diagnostic significance for IDD (AUC circRNA_104670 = 0.96; AUC miRNA-17-3p = 0.91). A significant correlation was detected between the Pfirrmann grade and expression of circRNA_104670 (r = 0.63; p = 0.00) and miR-17-3p (r = −0.62; p = 0.00). Flow-cytometric analysis and the MTT assay showed that interfering with circRNA_104670 using small interfering RNA (siRNA) inhibited NP cell apoptosis (p < 0.01), and this inhibition was reduced by interfering with miR-17-3p. Interfering with circRNA_104670 suppressed MMP-2 expression and increased extracellular matrix (ECM) formation, which were also reduced by interfering with miR-17-3p. Finally, an MRI evaluation showed that circRNA_104670 inhibition mice had a lower IDD grade compared with control mice (p < 0.01), whereas circRNA_104670 and miRNA-17-3p inhibition mice had a higher IDD grade compared with circRNA_104670 inhibition mice (p < 0.05). CircRNA_104670 is highly expressed in the NP tissues of IDD and acts as a ceRNA during NP degradation.

CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis

“…Several studies have confirmed that circRNAs are rich in miRNA binding sites and act as miRNA sponges to abolish the inhibition of miRNAs on their target genes in a mechanism called the competitive endogenous RNA (ceRNA) 24,25 . Increasing evidence indicates that circRNAs act as miRNA inhibitors in the development and progression of IVDD 18,19 .…”

“…Accordingly, cell metabolism, differentiation, proliferation, and survival involving these targeted mRNAs will be affected due to the biding of circRNAs and miRNAs 17 . Increasing evidence suggests the role of circRNAs in the pathogenesis of IVDD 18,19 . This study aimed to investigate the role of circRNAs in the pathogenesis of IVDD, and we selected circERCC2 based on bioinformatics analysis and explored its role in the regulation of mitophagy and apoptosis during the progression of IVDD.…”

A novel circFMN2 promotes tumor proliferation in CRC by regulating the miR-1182/hTERT signaling pathways

“…These results revealed that circFMN2 may act as a biomarker and therapeutic target for CRC. Increasing evidence shows that circRNAs have a range of functions including regulation of RNA binding proteins (RBPs), promotion of mRNA transcription in cis and post-transcriptional regulation through sponging of miRNAs [26][27][28]. MiRNAs are a class of non-coding small RNAs of approximately 19-23 nucleotides in length, which are widely involved in various biological behaviors of cancer cells [29].…”

Circular RNAs in nucleus pulposus cell function and intervertebral disc degeneration

“…Song et al performed circRNA microarray and identified circRNA_104670 as one of the highest upregulated circRNAs in degenerative NP tissues. Bioinformatic reconstruction of the regulatory network of circRNA_104670 revealed that this circRNA might act through the miR‐17‐3p‐matrix metallopeptidase (MMP)‐2 axis in NP cells.…”