LncRNA MAGI2-AS3 is down-regulated in intervertebral disc degeneration and participates in the regulation of FasL expression in nucleus pulposus cells

Cui, S T; Liu, Zizhen; Tang, Bin; Wang, Zhizhen; Li, Baojian

doi:10.1186/s12891-020-3086-y

Cited by 19 publications

(18 citation statements)

References 21 publications

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“…ligand expression levels in NP cells (8). lncRNA PART1 has been reported to be upregulated in the central nucleus pulposus tissue of patients with IDD (17).…”

Section: Role Of Lncrna Part1 In Intervertebral Disc Degeneration Andmentioning

confidence: 97%

“…The primary aim of clinical treatment for IDD is primarily associated with alleviating symptoms (7), though the specific mechanism of IDD pathogenesis and aetiology is not completely understood. There are three types of cells that have been reported to be involved in IDD, namely endplate chondrocytes cells, inner and outer annulus fibrosus cells and the internal nucleus pulposus (NP) cells (8)(9)(10). During IDD progression, a variety of inflammatory factors and extracellular matrix (ECM) degradation products accumulate in NP tissues, which affect NP cell physiology and function (11).…”

Section: Introductionmentioning

confidence: 99%

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Role of lncRNA PART1 in intervertebral disc degeneration and associated underlying mechanism

et al. 2020

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Intervertebral disc degeneration (IDD) is a chronic skeletal muscle degeneration disease. Previous studies have demonstrated that long non-coding RNAs (lncRNAs) exert significant roles in serious illnesses. Prostate androgen-regulated transcript 1 (PART1) is an identified lncRNA that has been reported to be a regulator in a number of diseases. However, the potential effects of PART1 in IDD have yet to be fully elucidated. The present study aimed to investigate the roles of lncRNA PART1 in IDD and identify a possible underlying mechanism. Human nucleus pulposus (NP) cells were first exposed to lipopolysaccharide (LPS) to construct in vitro IDD models. Reverse transcription-quantitative PCR (RT-qPCR) was performed to measure lncRNA PART1 expression levels in 10 ng/ml LPS-stimulated NP cells and normal cells (untreated cells). Dual-luciferase reporter assays were conducted to verify the possible binding sites of microRNA (miR)-190a-3p on lncRNA PART1. In addition, NP cell viability and apoptosis were measured by performing MTT and flow cytometry, respectively. Expression and secretion of inflammatory factors (TNF-α, IL-1β and IL-6) and extracellular matrix (ECM) degradation-related proteins (aggrecan and collagen type II) were measured using ELISA, RT-qPCR and western blotting. Expression levels of lncRNA PART1 in LPS-treated NP cells were found to be higher compared with those in the control groups. miR-190a-3p directly targeted lncRNA PART1. PART1 knockdown enhanced cell viability, reduced cell apoptosis, inhibited inflammatory factor secretion and promoted ECM degradation in LPS-stimulated NP cells. However, transfection with the miR-190a-3p inhibitor reversed the aforementioned PART1 knockdown-induced alterations in cell viability, apoptosis, inflammatory cytokine and ECM degradation. Collectively, these results suggest that PART1 accelerates the progression of IDD by directly targeting miR-190a-3p, which provides a novel target for IDD diagnosis and treatment.

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“…ligand expression levels in NP cells (8). lncRNA PART1 has been reported to be upregulated in the central nucleus pulposus tissue of patients with IDD (17).…”

Section: Role Of Lncrna Part1 In Intervertebral Disc Degeneration Andmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Role of lncRNA PART1 in intervertebral disc degeneration and associated underlying mechanism

et al. 2020

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“…For example, Chen et al [ 12 ] reported that LINC01121 act as a sponge of miR-150-5p to induced IVD progression. Cui et al [ 13 ] found that LncRNA MAGI2-AS3 is down-regulated in IVD, which was correlated with expression of FasL. LncRNA nuclear enriched abundant transcript 1 (NEAT1), a new lncRNA, has been demonstrated to serve an important role in cell apoptosis [ 14 ], non-small cell lung cancer invasion [ 15 ] and sepsis progression [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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

Cheng

Ma²,

et al. 2021

Eur J Med Res

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Background This study aimed to assess the role and mechanism of lncRNA NEAT1 in intervertebral disc degeneration (IVD). Methods LncRNA profile (GSE56081) between IVD and healthy control was downloaded from the Gene Expression Omnibus (GEO) database and analyzes differential lncRNA expression. Expression of lncRNA NEAT1 in IVD tissue and TNF-α/IL-1β-stimulated nucleus pulposus cells were further measured by RT-PCR. The lncRNA NEAT1 overexpression plasmids (pcDNA-NEAT1) were constructed and transfected into nucleus pulposus cells. Catabolic biomarkers (MMP-3 and MMP-13), anabolic biomarkers (Col II and Aggrecan) and Nrf2 expression were further measured. To further investigate the function of Nrf2, nucleus pulposus cells were pretreated with or without 25 μM tert-Butylhydroquinone (TBHQ), a Nrf2 activator, for 18 h and subsequently cotreated with pcDNA-NEAT1. Results A total of 1432 lncRNAs were differentially expressed in GSE56081. Bioinformatic analysis found that these lncRNAs mainly enriched in Nrf2/ARE signaling pathway. LncRNA NEAT1 was highly expressed in IVD tissues than that of healthy control. Moreover, TNF-α/IL-1β induced a time- and dose-dependent increase in the mRNA expression of lncRNA NEAT1 in the nucleus pulposus cells. Overexpression of lncRNA NEAT1 abates promotes nucleus pulposus cells proliferation but induces matrix degradation. Meanwhile, nucleus and cytoplasm Nrf2 expression was significantly down-regulated by lncRNA NEAT1 upregulation. Nrf2 activator (TBHQ) could partially reverse the inhibitory effects of overexpression of lncRNA NEAT1 on matrix degradation. Conclusion Collectively, our data unveiled the lncRNA NEAT1 promotes matrix degradation by regulating Nrf2/ARE signaling pathway, suggesting a potential therapeutic for IVD in the future.

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“…[16][17][18][19] Numerous lncRNAs were shown to be deregulated in many orthopedic diseases including osteosarcoma, scoliosis, osteonecrosis of the femoral head, rheumatoid arthritis and also IDD. [20][21][22][23][24][25] For example, Cui et al 26 reported that MAGI2-AS3 was decreased in IDD and was involved in FasL expression in NP cells. Zhao et al 27 found that LINC00958 induced matrix degradation and growth via modulating miR-203/SMAD3.…”

Section: Introductionmentioning

confidence: 99%

“…Numerous lncRNAs were shown to be deregulated in many orthopedic diseases including osteosarcoma, scoliosis, osteonecrosis of the femoral head, rheumatoid arthritis and also IDD 20–25 . For example, Cui et al 26 . reported that MAGI2‐AS3 was decreased in IDD and was involved in FasL expression in NP cells.…”

Section: Introductionmentioning

confidence: 99%

LINC01121 induced intervertebral disc degeneration via modulating miR‐150‐5p/MMP16 axis

Chen

et al. 2020

The Journal of Gene Medicine

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Background: Growing evidence indicates that Long noncoding RNAs contribute to cell differentiation, invasion, metabolism, proliferation and metastasis. However, the potential role of LINC01121 in progression of intervertebral disc degeneration (IDD) remains unclear. Methods: LINC01121, matrix metalloprotease (MMP)-16 and miR-150-5p expression was determined by a quantitative-reverse transcriptase-polymerase chain reaction assay. Inflammatory cytokines level was measured by an enzyme-linked immunosorbent assay and cell counting kit-8 analysis was used to assess cell proliferation. MMP-16-specific binding with miR-150-5p was verified with a luciferase reporter assay. Results: We noted that interleukin (IL)-1β and tumor necrosis factor (TNF)-α treatment enhanced LINC01121 and MMP-16 expression in nucleus pulposus (NP) cells. LINC01121 was higher in IDD specimens compared to that in control specimens. Higher expression of LINC01121 was correlated with disc degeneration degree. Ectopic expression of LINC01121 enhanced cell proliferation and promoted ki-67, MMP-3 and ADAMTS5 expression and also suppressed collagen II expression in NP cells. We observed that overexpression of LINC01121 increased the secretion of three inflammatory cytokines, including IL-6, TNF-α and IL-1β. We found that ectopic expression of LINC01121 decreased the miR-150-5p level in NP cells. Luciferase reporter data confirmed that MMP-16 was one direct target of miR-150-5p. Overexpression of miR-150-5p inhibited MMP-16 level and elevated the expression of LINC01121 enhanced MMP-16 level. We also found that MMP-16 was up-regulated in IDD specimens compared to that in control specimens. Higher expression of MMP-16 was correlated with disc degeneration degree. Interestingly, MMP-16 expression was positively related to LINC01121 in IDD specimens. Finally, overexpression of LINC01121 regulated cell growth, extracellular matrix degradation and inflammatory cytokine secretion via modulating MMP-16.

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LncRNA MAGI2-AS3 is down-regulated in intervertebral disc degeneration and participates in the regulation of FasL expression in nucleus pulposus cells

Cited by 19 publications

References 21 publications

Role of lncRNA PART1 in intervertebral disc degeneration and associated underlying mechanism

Role of lncRNA PART1 in intervertebral disc degeneration and associated underlying mechanism

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

LINC01121 induced intervertebral disc degeneration via modulating miR‐150‐5p/MMP16 axis

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