LncRNA NEAT1 promotes nucleus pulposus cell matrix degradation through regulating Nrf2/ARE axis

Cheng, Li; Ma, Xiaobo; Ni, Chenfei; Xu, Jingyan; Xie, Y J; Kan, Junwei; Wei, Xiaoli

doi:10.1186/s40001-021-00481-2

Cited by 10 publications

(5 citation statements)

References 30 publications

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“…Also, 11 widely regulated RNAs were screened. Of these, miR-185-5 P and NEAT1 have been shown to be associated with IDD progression ( Zhang H. et al, 2020 ; Li et al, 2021 ). The remaining genes have been shown to be involved in the pathological process of other diseases ( Ren et al, 2019 ; Tollenaere et al, 2019 ; Yang et al, 2019a ; Zhang et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Core Genes and Screening of Potential Targets in Intervertebral Disc Degeneration Using Integrated Bioinformatics Analysis

et al. 2022

Front. Genet.

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Background: Intervertebral disc degeneration (IDD), characterized by diverse pathological changes, causes low back pain (LBP). However, prophylactic and delaying treatments for IDD are limited. The aim of our study was to investigate the gene network and biomarkers of IDD and suggest potential therapeutic targets.Methods: Differentially expressed genes (DEGs) associated with IDD were identified by analyzing the mRNA, miRNA, and lncRNA expression profiles of IDD cases from the Gene Expression Omnibus (GEO). The protein–protein interaction (PPI) network, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis as well as miRNA–lncRNA–mRNA networks were conducted. Moreover, we obtained 71 hub genes and performed a comprehensive analysis including GO, KEGG, gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), Disease Ontology (DO), methylation analysis, receiver operating characteristic (ROC) curve analysis, immune infiltration analysis, and potential drug identification. We finally used qRT-PCR to verify 13 significant DEGs in normal and degenerative nucleus pulposus cells (NPCs).Results: We identified 305 DEGs closely related to IDD. The GO and KEGG analyses indicated that changes in IDD are significantly associated with enrichment of the inflammatory and immune response. GSEA analysis suggested that cell activation involved in the inflammatory immune response amide biosynthetic process was the key for the development of IDD. The GSVA suggested that DNA repair, oxidative phosphorylation, peroxisome, IL-6-JAK-STAT3 signaling, and apoptosis were crucial in the development of IDD. Among the 71 hub genes, the methylation levels of 11 genes were increased in IDD. A total of twenty genes showed a high functional similarity and diagnostic value in IDD. The result of the immune cell infiltration analysis indicated that seven genes were closely related to active natural killer cells. The most relevant targeted hub genes for potential drug or molecular compounds were MET and PIK3CD. Also, qRT-PCR results showed that ARHGAP27, C15orf39, DEPDC1, DHRSX, MGAM, SLC11A1, SMC4, and LINC00887 were significantly downregulated in degenerative NPCs; H19, LINC00685, mir-185-5p, and mir-4306 were upregulated in degenerative NPCs; and the expression level of mir-663a did not change significantly in normal and degenerative NPCs.Conclusion: Our findings may provide new insights into the functional characteristics and mechanism of IDD and aid the development of IDD therapeutics.

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Section: Discussionmentioning

confidence: 99%

Identification of Core Genes and Screening of Potential Targets in Intervertebral Disc Degeneration Using Integrated Bioinformatics Analysis

et al. 2022

Front. Genet.

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“… 33 LncRNAs can induce EMT by regulating transcription factors such as E-cadherin, N-cadherin, vimentin, β-catenin, Snail, slug, etc., or alter the extracellular matrix (ECM) by changing the activity of ECM degrading enzymes (matrix metallopeptidase, MMP). 34 In addition, it can activate the Wnt/β-catenin, PI3K/AKT, MAPK and other signaling pathways, thereby promoting the invasion and metastasis of malignant melanoma. 35 A recent study reported the role of oncogenic lncRNA LNCOC1 in ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

LncRNA LNCOC1 is Upregulated in Melanoma and Serves as a Potential Regulatory Target of miR-124 to Suppress Cancer Cell Invasion and Migration

Liu¹,

Ding²,

Wei³

et al. 2022

CCID

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Background A cascade of genes and pathways have been reported in the precise regulation of malignant melanoma (MM). Previous study has demonstrated that lncRNA LNCOC1 is an oncogenic factor in the pathogenesis and development of various cancers. The present study explored the functionalities of LNCOC1 and its interactions with miR-124 in MM. Methods A total of 65 melanoma patients were enrolled in this study. The expression of LNCOC1 and miR-124 after cell transfection were detected by RT-qPCR. The migration rates of SK-MEL-3 and A375 cells after transient transfection with LNCOC1 expression vector and miR-124 mimic was detected by trans-well assay. Results LNCOC1 was accumulated to high levels in melanoma, and it was significantly correlated with the low survival rate of melanoma patients. Our bioinformatics data showed that miR-124 could target LNCOC1. Overexpression of miR-124 could downregulate LNCOC1. However, up-regulated the expression of LNCOC1 did not affect the expression of miR-124. Our correlation analysis also revealed that the expression of LNCOC1 and miR-124 were inversely correlated in both melanoma tissues and non-tumor tissues. The trans-well invasion and migration assays indicated that overexpression of miR-124 inhibited the melanoma cell invasion and migration. However, overexpression of LNCOC1 promoted melanoma cell invasion and migration. Conclusion LNCOC1 is upregulated in melanoma, which can be considered as a potential target of miR-124 in modulating melanoma cell invasion and migration. LNCOC1 may also be an interfering target of MM therapy.

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“…NP cells were first separated from the nucleus pulposus of human intervertebral discs. An IDD cell model was established by treating NP cells with IL-1β (5, 10, 20, 50 ng/ml) [17] or H2O2 (10,25,50, 100 μM) [18] for 24 hours. IL-1β (Order No.…”

Section: Culture and Treatment Of Cellsmentioning

confidence: 99%

ZIP4 upregulation aggravates nucleus pulposus cell degradation by promoting inflammation and oxidative stress by mediating the HDAC4-FoxO3a axis

Shen,

Li,

Wang

et al. 2024

Aging

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Background: Extracellular matrix metabolism dysregulation in nucleus pulposus (NP) cells represents a crucial pathophysiological feature of intervertebral disc degeneration (IDD). Our study elucidates the role and mechanism of Testis expressed 11 (TEX11, also called ZIP4) extracellular matrix degradation in the NP. Materials and methods: Interleukin-1β (IL-1β) and H2O2 were used to treat NP cells to establish an IDD cell model. Normal NP tissues and NP tissues from IDD patients were harvested. ZIP4 mRNA and protein profiles in NP cells and tissues were examined. Enzyme-linked immunosorbent assay (ELISA) confirmed the profiles of TNF-α, IL-6, MDA, and SOD in NP cells. The alterations of reactive oxygen species (ROS), lactate dehydrogenase (LDH), COX2, iNOS, MMP-3, MMP-13, collagen II, aggrecan, FoxO3a, histone deacetylase 4 (HDAC4), Sirt1 and NF-κB levels in NP cells were determined using different assays. Results: The ZIP4 profile increased in the NP tissues of IDD patients and IL-1β-or H2O2-treated NP cells. ZIP4 upregulation bolstered inflammation and oxidative stress in NP cells undergoing IL-1β treatment and exacerbated their extracellular matrix degradation, whereas ZIP4 knockdown produced the opposite outcome. Mechanistically, ZIP4 upregulated HDAC4 and enhanced NF-κB phosphorylation while repressing Sirt1 and FoxO3a phosphorylation levels. HDAC4 knockdown or Sirt1 promotion attenuated the effects mediated by ZIP4 overexpression in NP cells. Conclusions: ZIP4 upregulation aggravates the extracellular matrix (ECM) degradation of NP cells by mediating inflammation and oxidative stress through the HDAC4-FoxO3a axis.

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LncRNA NEAT1 promotes nucleus pulposus cell matrix degradation through regulating Nrf2/ARE axis

Cited by 10 publications

References 30 publications

Identification of Core Genes and Screening of Potential Targets in Intervertebral Disc Degeneration Using Integrated Bioinformatics Analysis

Identification of Core Genes and Screening of Potential Targets in Intervertebral Disc Degeneration Using Integrated Bioinformatics Analysis

LncRNA LNCOC1 is Upregulated in Melanoma and Serves as a Potential Regulatory Target of miR-124 to Suppress Cancer Cell Invasion and Migration

ZIP4 upregulation aggravates nucleus pulposus cell degradation by promoting inflammation and oxidative stress by mediating the HDAC4-FoxO3a axis

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