Upregulation of P53 promotes nucleus pulposus cell apoptosis in intervertebral disc degeneration through upregulating NDRG2

Zhang, Kejie; Zhang, Yuanbin; Zhang, Cong; Zhu, Limin

doi:10.1002/cbin.11650

Cited by 13 publications

(14 citation statements)

References 28 publications

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“…HIF-1 promotes but P53 hinders these genes' expression (37,38). Moreover, HIF-1 and P53 show negative and positive regulatory effects on NDRG2, respectively (39)(40)(41)(42). Hence, we believe that the regulation of NDRG2 on glycolysis ux is accomplished by cooperating with C-Myc, HIF-1, and P53 to regulate the expression of glycolytic genes.…”

Section: Discussionmentioning

confidence: 91%

NDRG2 inhibits glycolysis in liver cancer cells is accompanied by the regulation of SIRT1

Xin

Cao

2022

Preprint

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NDRG2 is a tumor suppressor, highly expressed in normal tissues but down-regulated in many cancers. This enzyme was involved in glycolysis by regulating glycolytic enzymes in ccRCC and colorectal cancer. However, the mechanism of NDRG2 regulating glycolysis is still not clear, and the function of NDRG2 in liver tumor glycolysis is completely unknown. In the present study, we first demonstrated the low expression of NDRG2 in liver tumor tissues and found that the survival rate of patients was negatively correlated with the expression of NDRG2. Subsequently, based on NDRG2 overexpressed and knockdown cell lines, NDRG2 was shown to have the ability to inhibit glycolysis in liver cancer cells. Finally, SIRT1, a deacetylase that plays important role in glycolysis regulation, is negatively regulated by NDRG2 in liver tumors. Our data enrich the understanding of the role of NDRG2 in tumor growth and improve the mechanism by which NDRG2 regulates glycolysis.

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Section: Discussionmentioning

confidence: 91%

NDRG2 inhibits glycolysis in liver cancer cells is accompanied by the regulation of SIRT1

Xin

Cao

2022

Preprint

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“… 39 Moreover, as an apoptosis marker, elevated P53 stimulates apoptosis of nucleus pulposus cells and accelerates IVDD progression. 40 Previous clinical research revealed that the level of IL-1β in the IVD of IVDD patients was significantly elevated. 41 Mechanism study demonstrated that IL-1β accelerated the production of Caspase-3, P53 and Bax in IVD but reduced the production of anti-apoptotic proteins Bcl-2 as well as matrix proteins Col2 and aggrecan.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology and Experimental Validation to Reveal the Pharmacological Mechanisms of Liuwei Dihuang Decoction Against Intervertebral Disc Degeneration

Zhang¹,

Yao²,

Zhang³

et al. 2021

DDDT

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To explore the pharmacological mechanisms of Liuwei Dihuang Decoction (LWDHD) against intervertebral disc (IVD) degeneration (IVDD) via network pharmacology analysis combined with experimental validation. Methods: First, active ingredients and related targets of LWDHD, as well as related genes of IVDD, were collected from public databases. The protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed to predict the core targets and pathways of LWDHD against IVDD. Secondly, the IVDD model of mice treated with LWDHD was selected to validate the major targets predicted by network pharmacology. Results: By searching the intersection of the active ingredient targets and IVDD targets, a total of 110 targets matched the related targets of 30 active ingredients in LWDHD and IVDD were retrieved. PPI network analysis indicated that 17 targets, including Caspase-3, IL-1β, P53, etc., were hub targets. GO and KEGG enrichment analyses showed that the apoptosis pathway was enriched by multiple targets and served as the target for in vivo experimental study validation. The results of animal experiments revealed that LWDHD administration not only restored the decrease in disc height and abnormal degradation of matrix metabolism in IVDD mice but also reversed the high expression of Bax, Caspase-3, IL-1β, P53, and low expression of Bcl-2, thereby inhibiting the apoptosis of IVD tissue and ameliorating the progression of IVDD. Conclusion: Using a comprehensive network pharmacology approach, our findings predicted the active ingredients and potential targets of LWDHD intervention for IVDD, and some major target proteins involved in the predictive signaling pathway were validated experimentally, which gave us a new understanding of the pharmacological mechanism of LWDHD in treating IVDD at the comprehensive level.

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“…As reported (14), we induced the NPCs to become DNPCs to carry out the following molecular mechanism study. Moreover, because of technical and periodic reasons, we cannot establish a rat model of IDD as the previous study (28) to explore the molecular regulatory mechanism of DNPCs. At present, we only verified the results in existing cell lines.…”

Section: Discussionmentioning

confidence: 99%

miR-199a-5p regulates the proliferation and apoptosis of degenerative nucleus pulposus cells through the CDKN1B/NF-κB axis

2022

Shock

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Intervertebral disc degeneration is a multifactorial pathological disease. miR-199a-5p is exceedingly implicated in regulating degenerative nucleus pulposus cell (DNPC). We explored the roles of miR-199a-5p in DNPCs. Cell morphology and Collagen II-positive expression were observed. Cell proliferation, apoptosis, and Bax and Bcl-2 levels were assessed. miR-199a-5p inhibitor, pcDNA3.1-CDKN1B, or si-CDKN1B was transfected into DNPCs. miR-199a-5p and CDKN1B expressions were detected. The binding relationship between miR-199a-5p and CDKN1B was verified. DNPCs with silenced miR-199a-5p and CDKN1B were treated with PDTC. The nuclear factor-κB (NF-κB) pathway-related protein levels were detected. DNPCs showed decreased proliferation and promoted apoptosis. miR-199a-5p was highly expressed in DNPCs. miR-199a-5p knockdown increased DNPC proliferation and inhibited apoptosis. CDKN1B was repressed in DNPCs. miR-199a-5p targeted CDKN1B. CDKN1B knockdown partially abrogated the effects of miR-199a-5p inhibition on DNPC proliferation and apoptosis. In DNPCs, p65 was translocated to the nucleus, IκB protein phosphorylation level was increased, and the NF-κB pathway was activated. miR-199a-5p knockdown or CDKN1B overexpression repressed the NF-κB pathway activation. NF-κB pathway inhibitor promoted DNPC proliferation and inhibited apoptosis. Briefly, miR-199a-5p was upregulated in DNPCs. We discovered for the first time that miR-199a-5p silencing repressed the NF-κB pathway by promoting CDKN1B transcription, thus promoting DNPC proliferation and inhibiting apoptosis.

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Upregulation of P53 promotes nucleus pulposus cell apoptosis in intervertebral disc degeneration through upregulating NDRG2

Cited by 13 publications

References 28 publications

NDRG2 inhibits glycolysis in liver cancer cells is accompanied by the regulation of SIRT1

NDRG2 inhibits glycolysis in liver cancer cells is accompanied by the regulation of SIRT1

Network Pharmacology and Experimental Validation to Reveal the Pharmacological Mechanisms of Liuwei Dihuang Decoction Against Intervertebral Disc Degeneration

miR-199a-5p regulates the proliferation and apoptosis of degenerative nucleus pulposus cells through the CDKN1B/NF-κB axis

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