miR‐640 aggravates intervertebral disc degeneration via NF‐κB and WNT signalling pathway

Dong, Wengang; Li, Jun; Lv, Yang; Wang, Fei; Liu, Tao; Sun, Shu-Yu; Liao, Bo; Shu, Zhen; Qian, Jixian

doi:10.1111/cpr.12664

Cited by 63 publications

(43 citation statements)

References 44 publications

(74 reference statements)

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“…Previous research studies have demonstrated that several mirnas are dysregulated in idd, including mir-21, mir-10b, mir-640 and mir-27 (34)(35)(36)(37). mir-200c is upregulated in degenerative nP tissues (38).…”

Section: Discussionmentioning

confidence: 97%

MicroRNA‑25‑3p regulates human nucleus pulposus cell proliferation and apoptosis in intervertebral disc degeneration by targeting Bim

Zhao

Zheng

et al. 2020

Mol Med Rep

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intervertebral disc degeneration (idd) is a degenerative disease of the spine originating from the intervertebral disc. Micrornas (mirnas or mirs) are a group of endogenous small non-coding rnas that act on target genes and play a critical role in numerous biological processes. However, the underlying mechanism of mir-25-3p in idd remains unclear. Therefore, the present study aimed to explore the role of mir-25-3p in the pathogenesis of idd. The results demonstrated that mir-25-3p was downregulated in rat degenerative nucleus pulposus (nP) cells and that Bcl-2 interacting mediator of cell death (Bim) was a direct target of mir-25-3p. next, to investigate the effect of mir-25-3p on normal nP cell proliferation and apoptosis, nP cells were transfected with an mir-25-3p inhibitor, a negative control of mir-25-3p inhibitor, mir-25-3p inhibitor + control-small interference rna (sirna) or mir-25-3p inhibitor + Bim-sirna for 48 h and cell proliferation and apoptosis were then analyzed. The results demonstrated that the mir-25-3p inhibitor could decrease nP cell proliferation and induce cell apoptosis, and these effects were reversed by Bim-sirna. in addition, an in vitro cell model of idd was established by subjecting nP cells to 10 ng/ml interleukin (il)-1β for 24 h. Further experiments suggested that il-1β treatment induced a reduction in nP cell proliferation and an increase in cell apoptosis, which were prevented by the mir-25-3p mimic. all the effects of mir-25-3p mimic on il-1β-treated NP cells were significantly reversed by Bim upregulation. These findings suggested that miR-25-3p may be a novel therapeutic target for idd prevention.

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Section: Discussionmentioning

confidence: 97%

MicroRNA‑25‑3p regulates human nucleus pulposus cell proliferation and apoptosis in intervertebral disc degeneration by targeting Bim

Zhao

Zheng

et al. 2020

Mol Med Rep

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“…We speculated that the Ang-1/Tie-2 pathway downregulates miR-640 and GATAD2A expression through three mechanisms. First, Dong et al [ 28 ] identified several NFκB binding sites in the human GATAD2A promoter and showed that pro-inflammatory cytokines such as TNF-α upregulate miR-640 and GATAD2A expression in nucleus pulposus cells through NFκB. Our group and others have previously reported that the Ang-1/Tie-2 pathway inhibits NFκB activation in ECs through two distinct mechanisms [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 95%

“…miR-640 expression is elevated in cholangiocarcinoma, ovarian carcinoma, and lymphocytic leukemia cells [ 25 , 26 , 27 ]. Dong et al [ 28 ] reported that miR-640 expression is elevated in degenerative intervertebral tissues of humans and that pro-inflammatory cytokines such as the tumor necrosis factor (TNF-α) and interleukin-1 (IL-1β) induce miR-640 expression in nucleus pulposus cells. In the present study, we reported for the first time that miR-640 levels in ECs decreased significantly after several hours of exposure to Ang-1 and that this response was mediated through a Tie-2-dependent decrease in transcription of miR-640 precursor.…”

Section: Discussionmentioning

confidence: 99%

Roles of miR-640 and Zinc Finger Protein 91 (ZFP91) in Angiopoietin-1-Induced In Vitro Angiogenesis

Harel

Sanchez‐Gonzalez

Echavarría

et al. 2020

Cells

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Angiopoietin-1 (Ang-1) is a ligand of Tie-2 receptors that promotes angiogenesis. It has been established that regulatory loops exist between angiogenic growth factors and distinct pro or anti-angiogenic miRNAs, but the nature and the roles of Ang-1-regulated miRNAs remain unclear. In this study, we assessed the role of miR-640 in Ang-1-induced angiogenesis in human umbilical vein endothelial cells (HUVECs). Exposure to Ang-1 (300 ng/mL) from 6 to 72 h significantly decreased expression of mature miR-640, a response that was mediated by Tie-2 receptors and was also observed in response to Ang-2, the vascular endothelial growth factor, and transforming growth factor β. Increasing miR-640 levels using a mimic inhibited Ang-1-induced cell migration and capillary-like tube formation whereas inhibition of miR-640 enhanced these responses. Pull down assays of biotinylated miR-640 revealed that miR-640 directly targets Zinc Finger Protein 91 (ZFP91), an atypical E3-ubiquitin ligase. Ang-1 exposure induced ZFP91 expression through down-regulation of miR-640. Silencing of ZFP91 significantly inhibited Ang-1-induced cell migration and tube formation. We conclude that Ang-1 upregulates ZFP91 expression through transcriptional down-regulation of miR-640 and that ZFP91 plays important roles in the promotion of Ang-1-induced endothelial cell migration and differentiation.

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“…In the past, some miRNAs, like miR-184 [18] and miR-640 [19], are reported to be involved in regulation of nucleus pulposus cells apoptosis. Dong et al [19] found that miR-640 aggravates intervertebral disc degeneration via NF-κB and WNT signaling pathway. Cai et al [20] found that miR-15a could targeting MAP 3 K9 and might be considered as a novel therapeutic target for IVDD treatment.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of miR-660 protects nucleus pulposus cells from TNF-a-induced apoptosis by targeting serum amyloid A1

et al. 2020

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Background: Intervertebral disc degeneration (IVDD) is a well-known cause of lower back pain, which is induced by multiple factors including increased apoptosis and decreased survival of nucleus pulposus cells. In this study, we evaluate the effect and potential mechanism of miR-660 on the nucleus pulposus cells apoptosis induced by TNF-α. Methods: First, we collected tissue of nucleus pulposus from IVDD and healthy controls. General characteristic of the IVDD and healthy control was also collected. And, we also collected nucleus pulposus cells that stimulated by TNF-α or control. miRNA microarray was performed to identify the differentially expressed miRNAs. Apoptosis rate and miR-660 relative expression was measured after stimulated with different concentration of TNF-α to identify the optimal concentration of TNF-α. Second, we successfully constructed antigomiR-660 to block the miR-660 expression in nucleus pulposus cells and then stimulated with TNF-α (100 ng/ml, 12 h). The apoptosis rates and relative protein expression were then measured again. The target association between miR-660 and SAA1 was confirmed by dual-luciferase reporter. Results: There was no significant difference between the age (IVDD: 39 ± 10 years, healthy controls: 36 ± 7 years), BMI and sex between IVDD and healthy controls. Microarray analysis found that miR-660 was significantly upregulated in IVDD and TNF-α treated groups, which was further identified by PCR. We found that the rate of apoptosis and miR-660 expression increased with TNF-α concentration increased. Finally, TNF-a with 100 ng/ml was used for further experiment. Compared with TNF-α group, TNF-α + antigomiR-660 could significantly downregulated the apoptosis rate and relative protein (c-Caspase3 and c-Caspase7). Dual-luciferase reporter revealed that miR-660 could directly binding to the SAA1 at 80-87 sites. Compared with TNF-α alone group, TNF-α + antigomiR-660 significantly up-regulated the SAA1 expression (P < 0.05). Conclusion: These results indicated that knockdown of miR-660 protected the nucleus pulposus from apoptosis that induced TNF-α via up-regulation of SAA1. Further studies should focus on the role of miR-660 in protecting IVDD in vivo.

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miR‐640 aggravates intervertebral disc degeneration via NF‐κB and WNT signalling pathway

Cited by 63 publications

References 44 publications

MicroRNA‑25‑3p regulates human nucleus pulposus cell proliferation and apoptosis in intervertebral disc degeneration by targeting Bim

MicroRNA‑25‑3p regulates human nucleus pulposus cell proliferation and apoptosis in intervertebral disc degeneration by targeting Bim

Roles of miR-640 and Zinc Finger Protein 91 (ZFP91) in Angiopoietin-1-Induced In Vitro Angiogenesis

Knockdown of miR-660 protects nucleus pulposus cells from TNF-a-induced apoptosis by targeting serum amyloid A1

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