scholarly journals Circular RNA hsa_circ_0001658 Inhibits Intervertebral Disc Degeneration Development by Regulating hsa-miR-181c-5p/FAS

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Ge-dong Meng ◽  
Bao-shan Xu
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Noncoding Rna ◽  
Intervertebral Disc Degeneration ◽  
Neural Progenitor Cells ◽  
Death Receptor ◽  
Circular Rna ◽  
Gene Expression Omnibus ◽  
Proliferation And Apoptosis ◽  
Human Neural Progenitor Cells

Background and Purpose. Intervertebral disc degeneration (IDD) is the main cause of low back pain, but its pathogenesis has not been studied clearly. Circular RNA is a type of noncoding RNA (ncRNA). In this study, we studied the potential role of circular RNA in the pathogenesis of IDD. Methods. We obtained microarray data (GSE116726, GSE67566) from Gene Expression Omnibus database, and differential expression level of ncRNA in nucleus pulposus (NP) tissues of IDD patients was analyzed. The potential circRNA-miRNA-mRNA regulatory network was analyzed by starBase. The effect of the interaction between hsa_circ_0001658, hsa-miR-181c-5p, and FAS on the proliferation and apoptosis of human neural progenitor cells (hNPCs) was studied. Results. hsa_circ_0001658 was significantly upregulated ( logFC > 2.0 and adj . P . Val < 0.01 ) in the NP tissues of IDD patients, and hsa-miR-181c-5p expression was downregulated ( logFC < − 2.0 and adj . P . Val < 0.01 ). Silencing of hsa-miR-181c-5p or overexpression of hsa_circ_0001658 inhibited the proliferation of hNPCs and promoted their apoptosis. hsa_circ_0001658 acted as a sponge of hsa-miR-181c-5p. hsa-miR-181c-5p downregulated the expression of Fas cell surface death receptor (FAS), promoted the proliferation, and inhibited the apoptosis of hNPCs. hsa_circ_0001658 functioned in hNPCs through targeting hsa-miR-181c-5p/FAS. Conclusion. Circular RNA hsa_circ_0001658 inhibits IDD development by regulating hsa-miR-181c-5p/FAS. It is expected to be a potential target for the therapy of IDD.

scholarly journals Circular RNA hsa_circ_0001658 Inhibits Intervertebral Disc Degeneration Development by Regulating hsa-miR-181c-5p/FAS

2021 ◽  
Author(s):  
Ge-dong Meng ◽  
Baoshan Xu
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Neural Progenitor Cells ◽  
Circular Rna ◽  
Gene Expression Omnibus ◽  
Non Coding Rna ◽  
Proliferation And Apoptosis ◽  
Human Neural Progenitor Cells

Abstract Background and purpose: Intervertebral disc degeneration (IDD) is the main cause of low back pain, but its pathogenesis has not been studied clearly. Circular RNA is a type of non-coding RNA (ncRNA). In this study, we aim to study the potential role of circular RNA in the pathogenesis of IDD. Methods: We obtained microarray data (GSE116726, GSE67566) from Gene Expression Omnibus database, and differentially analyzed ncRNA in nucleus pulposus (NP) tissues of IDD patients. The potential circRNAs-miRNAs-mRNAs regulatory network was analyzed by starBase. The effect of the interaction between hsa_circ_0001658, hsa-miR-181c-5p and FAS on the proliferation and apoptosis of human neural progenitor cells (hNPCs) were studied. Results:Hsa_circ_0001658 was significantly up-regulated (logFC>2.0 and adj.P.Val<0.01) in the NP tissues of IDD patients, and hsa-miR-181c-5p expression was down-regulated (logFC<-2.0 and adj.P.Val<0.01). Silencing of hsa-miR-181c-5p or overexpression of hsa_circ_0001658 inhibited the proliferation of hNPCs and promoted their apoptosis. Hsa_circ_0001658 acted as a sponge of hsa-miR-181c-5p. Hsa-miR-181c-5p down-regulated the expression of FAS, promoted the proliferation and inhibited the apoptosis of hNPCs. Hsa_circ_0001658 functioned in hNPCs through targeting hsa-miR-181c-5p/FAS.Conclusion:Circular RNA hsa_circ_0001658 inhibits intervertebral disc degeneration development by regulating hsa-miR-181c-5p/FAS. It is expected to be a potential target for the therapy of IDD.

scholarly journals A novel circRNA–miRNA–mRNA network reveals hsa-circ-0040039 as a biomarker for intervertebral disc degeneration

2021 ◽  
Vol 49 (12) ◽  
pp. 030006052096098
Author(s):  
Jianhua Tang ◽  
Chenlin Zhang ◽  
Shengru Wang ◽  
Jianfeng Chen
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Target Genes ◽  
Coagulation Factor ◽  
Circular Rna ◽  
Change Score ◽  
Intervertebral Discs ◽  
Gene Expression Omnibus ◽  
And Function

Objective Alterations in the structure and function of intervertebral discs by multifaceted chronic processes can result in intervertebral disc degeneration (IDD). The mechanisms involved in IDD are still unknown. Methods We investigated the possible mechanisms underlying IDD using a bioinformatics analysis of publicly available microarray expression datasets and built a circular RNA–microRNA–mRNA (circRNA–miRNA–mRNA) network based on the results. Datasets GSE67566 and GSE116726 were downloaded from the Gene Expression Omnibus (GEO) and analyzed using the limma package in R. The CircInteractome database was used to detect miRNAs related to circRNA, and TargetScan, miRDB, and miRTarBase were used to predict target mRNAs. Key target genes were annotated using Gene Ontology terms. Results The circRNA hsa-circ-0040039 was found to have the top log fold-change score. Analysis using Metascape showed that the associated genes were enriched mainly in the cell cycle. The Cytoscape plugin MCODE predicted that two members of the RAS oncogene family—RAB1A and RAB1B—and multiple coagulation factor deficiency (MCFD2) may play key roles in IDD. Conclusion Our results suggested that hsa-circ-0040039 and the related network may be potential biomarkers for IDD.

The noncoding RNA linc-ADAMTS5 cooperates with RREB1 to protect from intervertebral disc degeneration through inhibiting ADAMTS5 expression

2017 ◽  
Vol 131 (10) ◽  
pp. 965-979 ◽  
Author(s):  
Kun Wang ◽  
Yu Song ◽  
Wei Liu ◽  
Xinghuo Wu ◽  
Yukun Zhang ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Histone Deacetylases ◽  
Noncoding Rna ◽  
Intervertebral Disc Degeneration ◽  
Physical Interaction ◽  
Loss Of Function ◽  
Element Binding Protein ◽  
Long Intergenic Noncoding Rna

Previous studies have indicated the important roles of ADAMTS5 in intervertebral disc degeneration (IDD). However, the mechanisms that regulate ADAMTS5 expression in nuclear pulposus (NP) cells remain largely unknown. Evidence suggests that intergenic transcription may be associated with genes that encode transcriptional regulators. Here, we identified a long intergenic noncoding RNA, linc-ADAMTS5, which was transcribed in the opposite direction to ADAMTS5. In the present study, through mining computational algorithm programs, and publicly available data sets, we identified Ras-responsive element-binding protein 1 (RREB1) as a crucial transcription factor regulating the expression of ADAMTS5 in NP cells. RNA pull-down, RNA immunoprecipitation (RIP), in vitro binding assays, and gain- and loss-of-function studies indicated that a physical interaction between linc-ADAMTS5 and splicing factor proline/glutamine-rich (SFPQ) facilitated the recruitment of RREB1 to binding sites within the ADAMTS5 promoter to induce chromatin remodeling. This resulted in subdued ADAMTS5 levels in cultured NP cells involving histone deacetylases (HDACs). In clinical NP tissues, linc-ADAMTS5 and RREB1 were correlated negatively with ADAMTS5 expression. Taken together, these results demonstrate that RREB1 cooperates with noncoding RNA linc-ADAMTS5 to inhibit ADAMTS5 expression, thereby affecting degeneration of the extracellular matrix (ECM) of the intervertebral disc (IVD).

scholarly journals Mechanism of Long Noncoding RNA HOTAIR in Nucleus Pulposus Cell Autophagy and Apoptosis in Intervertebral Disc Degeneration

2022 ◽  
Vol 2022 ◽  
pp. 1-18
Author(s):  
Shujun Zhang ◽  
Sheng Song ◽  
Wei Cui ◽  
Xueguang Liu ◽  
Zhenzhong Sun
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Noncoding Rna ◽  
Intervertebral Disc Degeneration ◽  
Intervertebral Discs ◽  
Luciferase Reporter ◽  
Blue Staining ◽  
Tunel Staining ◽  
Lncrna Hotair

Objective. Intervertebral disc degeneration (IDD) contributes to cervical and lumbar diseases. Long noncoding RNAs (lncRNAs) are implicated in IDD. This study explored the mechanism of lncRNA HOTAIR in IDD. Methods. Normal and degenerative nucleus pulposus (NP) cells were isolated from NP tissues obtained in intervertebral disc surgery. Cell morphology was observed by immunocytochemistry staining and toluidine blue staining. NP cell markers were detected by RT-qPCR. Proliferation was detected by MTT assay. Autophagy-related proteins were detected by Western blot. Autophagosome was observed by monodansylcadaverine fluorescence staining. Apoptosis was detected by TUNEL staining and flow cytometry. si-HOTAIR and/or miR-148a inhibitor was introduced into degenerative NP cells. Binding relationships among HOTAIR, miR-148a, and PTEN were predicted and verified by dual-luciferase reporter assay and RNA pull-down. Finally, IDD rat models were established. Rat caudal intervertebral discs were assessed by HE staining. Expressions of HOTAIR, miR-148a, and PTEN were determined by RT-qPCR. Results. HOTAIR was highly expressed in degenerative NP cells p < 0.05 . si-HOTAIR inhibited degenerative NP cell apoptosis and autophagy p < 0.05 . HOTAIR upregulated PTEN as a sponge of miR-148a. miR-148a was poorly expressed in degenerative NP cells. miR-148a deficiency partially reversed the inhibition of si-HOTAIR on degenerative NP cell autophagy and apoptosis (all p < 0.05 ). In vivo assay confirmed that si-HOTAIR impeded autophagy and apoptosis in intervertebral disc tissues, thus improving pathological injury in IDD rats (all p < 0.05 ). Conclusion. LncRNA HOTAIR promoted NP cell autophagy and apoptosis via promoting PTEN expression as a ceRNA of miR-148a in IDD.

scholarly journals Emerging evidence on noncoding-RNA regulatory machinery in intervertebral disc degeneration: a narrative review

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Hao-Yu Guo ◽  
Ming-Ke Guo ◽  
Zhong-Yuan Wan ◽  
Fang Song ◽  
Hai-Qiang Wang
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Noncoding Rna ◽  
Regulatory Networks ◽  
Intervertebral Disc Degeneration ◽  
Target Genes ◽  
Noncoding Rnas ◽  
Circular Rnas ◽  
Form Complex ◽  
Underlying Mechanisms

AbstractIntervertebral disc degeneration (IDD) is the most common cause of low-back pain. Accumulating evidence indicates that the expression profiling of noncoding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long noncoding RNAs (lncRNAs), are different between intervertebral disc tissues obtained from healthy individuals and patients with IDD. However, the roles of ncRNAs in IDD are still unclear until now. In this review, we summarize the studies concerning ncRNA interactions and regulatory functions in IDD. Apoptosis, aberrant proliferation, extracellular matrix degradation, and inflammatory abnormality are tetrad fundamental pathologic phenotypes in IDD. We demonstrated that ncRNAs are playing vital roles in apoptosis, proliferation, ECM degeneration, and inflammation process of IDD. The ncRNAs participate in underlying mechanisms of IDD in different ways. MiRNAs downregulate target genes’ expression by directly binding to the 3′-untranslated region of mRNAs. CircRNAs and lncRNAs act as sponges or competing endogenous RNAs by competitively binding to miRNAs and regulating the expression of mRNAs. The lncRNAs, circRNAs, miRNAs, and mRNAs widely crosstalk and form complex regulatory networks in the degenerative processes. The current review presents novel insights into the pathogenesis of IDD and potentially sheds light on the therapeutics in the future.

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