LINC00969 promotes the degeneration of intervertebral disk by sponging miR‐335‐3p and regulating NLRP3 inflammasome activation

Yu, Lei; Hao, Yingjie; Xu, Chaojun; Zhu, Guangfa; Cai, Yingchun

doi:10.1002/iub.1989

Cited by 44 publications

(35 citation statements)

References 21 publications

(20 reference statements)

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“…Emerging studies indicate that lncRNAs are important regulators of NP cells. For example, lncRNA FAM83H-AS1 promotes the growth of NP cells through the Notch signaling pathway (19); LINC00969 promotes the development of IDD by targeting miR-335-3p and regulating NLRP3 inflammasome activation (20). In the present study, it was observed that PART1 was upregulated in degenerative NP tissues from patients with Idd, bulging and herniated discs, suggesting a potential role for PART1 in the degeneration of NP cells.…”

Section: Discussionsupporting

confidence: 49%

Long non-coding RNA PART1 promotes intervertebral disc degeneration through regulating the�miR‑93/MMP2 pathway in nucleus pulposus cells

2020

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The aim of the present study was to investigate the role of the long non-coding (lnc)RNA PART1 in nucleus pulposus (NP) cells derived from patients with intervertebral disc degeneration (Idd). The level of PART1 in degenerative NP tissues from patients with Idd, bulging and herniated discs was measured by reverse transcription-quantitative PcR (RT-qPcR) analysis. NP cells were isolated from patients with Idd and transfected with siPART1, after which time the growth ability of the NP cells was evaluated by cell counting Kit-8 and colony formation assays, and cell apoptosis was measured by flow cytometry. The levels of the cell proliferation marker Ki-67 and the apoptosis marker cleaved caspase-3, and the levels of genes related to extracellular matrix (EcM) synthesis and degradation, were also evaluated by western blotting and RT-qPcR, as appropriate. Bioinformatics methods predicted that miR-93 was sponged by PART1, and matrix metallopeptidase (MMP)2 was targeted by miR-93, which was further confirmed by dual-luciferase reporter assay. The levels of miR-93 and MMP2 were also measured in NP tissues, and further rescue experiments were performed to confirm the role of the PART1/miR-93/MMP2 pathway in NP cells. PART1 was found to be upregulated in degenerative NP tissues, and siPART1 caused an increase in cell growth ability and EcM synthesis, whereas it decreased cell apoptosis and EcM degradation in NP cells. miR-93 was downregulated and MMP2 was upregulated in degenerative NP tissues. Rescue experiments indicated that the effects of miR-93 inhibitor on NP cells were abolished by siPART1, and the effect of miR-93 mimic on NP cells was rescued by MMP2 overexpression. Thus, the results of the present study demonstrated that PART1 may regulate NP cell degeneration through the miR-93/MMP2 pathway. These findings indicate a novel signaling axis in NP cells that may be explored for the treatment of Idd.

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Section: Discussionsupporting

confidence: 49%

Long non-coding RNA PART1 promotes intervertebral disc degeneration through regulating the�miR‑93/MMP2 pathway in nucleus pulposus cells

2020

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“…In our study, we constructed the coexpression subnet of DAPK1-IT1 and function was analyzed with KEGG pathway (Fig. 6), found may function with Terpenoid backbone biosynthesis, Steroid biosynthesis, Vitamin digestion and absorption, Protein processing in endoplasmic reticulum, Phagosome, and some of these pathways have been proved to be involved in the occurrence and [46]. We will conduct further clinical studies on other lincRNAs in the future.…”

Section: Discussionmentioning

confidence: 97%

Analysis of long non-coding RNA expression profiles in high-glucose treated vascular endothelial cells

et al. 2020

BMC Endocr Disord

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Background: Diabetes mellitus is often associated with microvascular and macrovascular lesions, and hyperglycemia-induced vascular endothelial cell damage is a key factor. Methods: We investigated long non-coding RNAs (lncRNAs) and mRNAs that are affected by hyperglycemiainduced damage using human umbilical vein endothelial cells (HUVECs) as a model. HUVECs were cultured under high (25 mmol/L) or normal (5 mmol/L) glucose conditions for 6 d, and then lncRNAs and protein-coding transcripts were profiled by RNA-seq. Result: Among 40,379 lncRNAs screened, 214 were upregulated (log2 [fold-change] > 1, FDR < 0.05) and 197 were downregulated (log2 [fold-change] < − 1, FDR < 0.05) in response to high-glucose. Furthermore, among 28,431 proteincoding genes screened, 778 were upregulated and 998 were downregulated. A total of 945 lncRNA/mRNA pairs were identified, including 126 differentially expressed lncRNAs predicted to target 201 mRNAs, among which 26 were cisregulatory interactions. The corresponding lncRNA-mRNA network was composed of 354 lncRNA nodes, 1167 mRNA nodes and 9735 edges. Dozens of lncRNAs with high degree may play important roles in high-glucose-induced HUVEC damage, including ENST00000600527,

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“…In addition, NLRP3 inflammasome‐mediated pyroptosis can be negatively regulated by honokiol and activated by advanced glycation end products in NP cells (Song et al, 2017; Tang et al, 2018). LINC00969, a long noncoding RNA, also influences NLRP3 inflammation activation by regulating miR‐335‐3p (Yu, Hao, Xu, Zhu, & Cai, 2018). BRD4 plays essential roles in many diseases, such as virus‐induced airway inflammation and spinal cord injury (Rudman et al, 2018; Tian et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Bromodomain‐containing protein 4 inhibition alleviates matrix degradation by enhancing autophagy and suppressing NLRP3 inflammasome activity in NP cells

Hong

Markova

et al. 2020

Journal Cellular Physiology

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An imbalance between matrix synthesis and degradation is the hallmark of intervertebral disc degeneration while inflammatory cytokines contribute to the imbalance. Bromodomain and extra‐terminal domain (BET) family is associated with the pathogenesis of inflammation, and inhibition of BRD4, a vital member of BET family, plays an anti‐inflammatory role in many diseases. However, it remains elusive whether BRD4 plays a similar role in nucleus pulposus (NP) cells and participates in the pathogenesis of intervertebral disc degeneration. The present study aims to observe whether BRD4 inhibition regulates matrix metabolism by controlling autophagy and NLRP3 inflammasome activity. Besides, the relationship was investigated among nuclear factor κB (NF‐κB) signaling, autophagy and NLRP3 inflammasome in NP cells. Here, real‐time polymerase chain reaction, western blot analysis and adenoviral GFP‐LC3 vector transduction in vitro were used, and it was revealed that BRD4 inhibition alleviated the matrix degradation and increased autophagy in the presence or absence of tumor necrosis factor α. Moreover, p65 knockdown or treatment with JQ1 and Bay11‐7082 demonstrated that BRD4 inhibition attenuated NLRP3 inflammasome activity through NF‐κB signaling, while autophagy inhibition by bafilomycin A1 promoted matrix degradation and NLRP3 inflammasome activity in NP cells. In addition, analysis of BRD4 messenger RNA expression in human NP tissues further verified the destructive function of BRD4. Simply, BRD4 inhibition alleviates matrix degradation by enhancing autophagy and suppressing NLRP3 inflammasome activity through NF‐κB signaling in NP cells.

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LINC00969 promotes the degeneration of intervertebral disk by sponging miR‐335‐3p and regulating NLRP3 inflammasome activation

Cited by 44 publications

References 21 publications

Long non-coding RNA PART1 promotes intervertebral disc degeneration through regulating the�miR‑93/MMP2 pathway in nucleus pulposus cells

Long non-coding RNA PART1 promotes intervertebral disc degeneration through regulating the�miR‑93/MMP2 pathway in nucleus pulposus cells

Analysis of long non-coding RNA expression profiles in high-glucose treated vascular endothelial cells

Bromodomain‐containing protein 4 inhibition alleviates matrix degradation by enhancing autophagy and suppressing NLRP3 inflammasome activity in NP cells

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