CircRNA circ_SEC24A upregulates DNMT3A expression by sponging miR-26b-5p to aggravate osteoarthritis progression

Zhang, Zhongqiang; Yang, Bo; Zhou, Shuping; Wu, Junxing

doi:10.1016/j.intimp.2021.107957

Cited by 15 publications

(13 citation statements)

References 25 publications

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“…Therefore, it is crucial to explore the potential pathogenic mechanisms underlying IVDD. Recent studies have revealed that multiple differential methylation sites in IVDD are associated with human disc degeneration 14 and that DNMT3a modifications regulate various musculoskeletal disorders 35,36 . In this study, we first revealed that DNMT3a levels increased and PPARγ levels decreased gradually during the IVDD progression, suggesting an underlying regulatory relationship.…”

Section: Discussionmentioning

confidence: 64%

DNMT3a‐mediated methylation of PPARγ promote intervertebral disc degeneration by regulating the NF‐κB pathway

Cheng,

Wei,

Chen

et al. 2023

J Cellular Molecular Medi

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Intervertebral disc degeneration (IVDD) is a common chronic musculoskeletal disease that causes chronic low back pain and imposes an immense financial strain on patients. The pathological mechanisms underlying IVDD have not been fully elucidated. The development of IVDD is closely associated with abnormal epigenetic changes, suggesting that IVDD progression may be controlled by epigenetic mechanisms. Consequently, this study aimed to investigate the role of epigenetic regulation, including DNA methyltransferase 3a (DNMT3a)‐mediated methylation and peroxisome proliferator‐activated receptor γ (PPARγ) inhibition, in IVDD development. The expression of DNMT3a and PPARγ in early and late IVDD of nucleus pulposus (NP) tissues was detected using immunohistochemistry and western blotting analyses. Cellularly, DNMT3a inhibition significantly inhibited IL‐1β‐induced apoptosis and extracellular matrix (ECM) degradation in rat NP cells. Pretreatment with T0070907, a specific inhibitor of PPARγ, significantly reversed the anti‐apoptotic and ECM degradation effects of DNMT3a inhibition. Mechanistically, DNMT3a modified PPARγ promoter hypermethylation to activate the nuclear factor‐κB (NF‐κB) pathway. DNMT3a inhibition alleviated IVDD progression. Conclusively, the results of this study show that DNMT3a activates the NF‐κB pathway by modifying PPARγ promoter hypermethylation to promote apoptosis and ECM degradation. Therefore, we believe that the ability of DNMT3a to mediate the PPARγ/NF‐κB axis may provide new ideas for the potential pathogenesis of IVDD and may become an attractive target for the treatment of IVDD.

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Section: Discussionmentioning

confidence: 64%

DNMT3a‐mediated methylation of PPARγ promote intervertebral disc degeneration by regulating the NF‐κB pathway

Cheng,

Wei,

Chen

et al. 2023

J Cellular Molecular Medi

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“…Moreover, the indirect regulation of Dnmt3a by circRNAs has been observed in studies of OA. Zhang et al, (2021) revealed that circ_SEC24A expression is upregulated in osteoarthritic cartilage tissues and IL-1β-treated chondrocytes, and this upregulation is accompanied by miR-26b-5p downregulation and Dnmt3a upregulation. Zhu H. et al, (2021) demonstrated that circ-136474 downregulation and miR-766–3p upregulation exert chondroprotective effects against IL-1β-induced oxidative stress by suppressing Dnmt3a expression.…”

Section: Discussionmentioning

confidence: 99%

“… Zhu et al, (2020) reported that circGCN1L1 induces inflammation in TMJ synoviocytes and decreases anabolism of the extracellular matrix through miR-330–3p and TNF-α. Our ceRNA network revealed that ciRNA166 and circRNA1531 can combine with miR-9a-5p to regulate the target gene Dnmt3a, which plays an important regulatory role in apoptosis, ECM degradation, and chondrocyte injury in osteoarthritis ( Ma et al, 2019 ; Zhu H. et al, 2021 ; Zhang et al, 2021 ). Moreover, the indirect regulation of Dnmt3a by circRNAs has been observed in studies of OA.…”

Section: Discussionmentioning

confidence: 99%

Whole-transcriptome sequencing and ceRNA interaction network of temporomandibular joint osteoarthritis

An²,

Zhou³

et al. 2022

Front. Genet.

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Purpose: The aim of this study was to conduct a comprehensive transcriptomic analysis to explore the potential biological functions of noncoding RNA (ncRNAs) in temporomandibular joint osteoarthritis (TMJOA).Methods: Whole transcriptome sequencing was performed to identify differentially expressed genes (DEGs) profiles between the TMJOA and normal groups. The functions and pathways of the DEGs were analyzed using Metascape, and a competitive endogenous RNA (ceRNA) network was constructed using Cytoscape software.Results: A total of 137 DEmRNAs, 65 DEmiRNAs, 132 DElncRNAs, and 29 DEcircRNAs were identified between the TMJOA and normal groups. Functional annotation of the DEmRNAs revealed that immune response and apoptosis are closely related to TMJOA and also suggested key signaling pathways related to TMJOA, including chronic depression and PPAR signaling pathways. We identified vital mRNAs, including Klrk1, Adipoq, Cryab, and Hspa1b. Notably, Adipoq expression in cartilage was significantly upregulated in TMJOA compared with normal groups (10-fold, p < 0.001). According to the functional analysis of DEmRNAs regulated by the ceRNA network, we found that ncRNAs are involved in the regulation of autophagy and apoptosis. In addition, significantly DEncRNAs (lncRNA-COX7A1, lncRNA-CHTOP, lncRNA-UFM1, ciRNA166 and circRNA1531) were verified, and among these, circRNA1531 (14.5-fold, p < 0.001) and lncRNA-CHTOP (14.8-fold, p < 0.001) were the most significantly downregulated ncRNAs.Conclusion: This study showed the potential of lncRNAs, circRNAs, miRNAs, and mRNAs may as clinical biomarkers and provides transcriptomic insights into their functional roles in TMJOA. This study identified the transcriptomic signatures of mRNAs associated with immunity and apoptosis and the signatures of ncRNAs associated with autophagy and apoptosis and provides insight into ncRNAs in TMJOA.

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“…Recently, ceRNA (circRNA–miRNA–mRNA) has been reported to play an important role in cell proliferation, cell differentiation, ECM synthesis and degradation, immune response, and growth and development [ 16 , 17 , 18 , 19 , 20 ]. Studies have shown that the circ-0005526/miR-142-5p/TCF4, circ-UBE2G1/miR-373/HIF-1α, circ-0000423/miR-27b-3p/MMP-13, and circ-SEC24A/miR-26b-5p/DNMT3A regulatory axis can promote inflammatory factor-induced chondrocytes apoptosis and extracellular matrix degradation [ 18 , 21 , 22 , 23 ]. Then, the circ-LRP1B/miR-34a-5p/NRF1 regulatory axis can promote chondrocytes proliferation and inhibit their apoptosis [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Integration Analysis of circRNA–miRNA–mRNA and Identification of Critical Networks in Valgus-Varus Deformity (Gallus gallus)

Cai

et al. 2023

Genes

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Valgus-valgus deformity (VVD) is a common leg deformity in broilers with inward or outward deviation of the tibiotarsus and tarsometatarsus. The competing endogenous RNA (ceRNA) network plays an essential role in the study of leg disease. However, its role in the etiology and pathogenesis of VVD remains unclear. Here, based on case (VVD) and control (normal) group design, we performed analyses of differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs) and differentially expressed mRNAs (DEmRNAs). Transcriptome data derived 86 DEcircRNAs, 13 DEmiRNAs and 410 DEmRNAs. Functional analysis showed that DEmRNAs were significantly enriched in cell cycle, apoptosis, ECM-receptor interaction, FoxO signaling pathway and protein processing synthesis. DEcirc/miRNA-associated DEmRNAs were associated with skeletal and muscle growth and development pathways, including mTOR, Wnt, and VEGF signaling pathways. Subsequently, a circRNA–miRNA–mRNA regulatory network was constructed based on the ceRNA hypothesis, including 8 circRNAs, 6 miRNAs, and 31 mRNAs, which were significantly enriched in the skeletal developmental pathway. Finally, two key mRNAs (CDC20 and CTNNB1) and their regulatory axes were screened by the PPI network and cytohubba. The expression levels of CDC20 and CTNNB1 in cartilage and seven other tissues were also quantified by qPCR. In conclusion, we analyzed the functions of DEmRNA, DEcircRNA and DEmiRNA and constructed the hub ceRNA regulatory axis, and obtained two hub genes, CDC20 and CTNNB1. The study more deeply explored the etiology and pathogenesis of VVD and lays the foundation for further study of the role of the ceRNA network on skeletal development.

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CircRNA circ_SEC24A upregulates DNMT3A expression by sponging miR-26b-5p to aggravate osteoarthritis progression

Cited by 15 publications

References 25 publications

DNMT3a‐mediated methylation of PPARγ promote intervertebral disc degeneration by regulating the NF‐κB pathway

DNMT3a‐mediated methylation of PPARγ promote intervertebral disc degeneration by regulating the NF‐κB pathway

Whole-transcriptome sequencing and ceRNA interaction network of temporomandibular joint osteoarthritis

Integration Analysis of circRNA–miRNA–mRNA and Identification of Critical Networks in Valgus-Varus Deformity (Gallus gallus)

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