High Expression of PHGDH Predicts Poor Prognosis in Non–Small Cell Lung Cancer

Zhu, Jinhong; Ma, Jianqun; Wang, Xudong; Ma, Tiangang; Zhang, Shu; Wang, Wei; Zhou, Xiaoyu; Shi, Jiahai

doi:10.1016/j.tranon.2016.08.003

Cited by 64 publications

(48 citation statements)

References 34 publications

(60 reference statements)

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“…SNP rs72699833 is located on chromosome 1 and is associated in cis with PHGDH, a gene involved in the metabolism of serine that is overexpressed in some subtypes of breast, cervical, colorectal and non-small-cell lung cancer, and in these diseases generally associated with a poorer outcome. [37][38][39][40] In addition, rs72699833 is associated through our eQTL analysis in trans with five other genes: LAD1 on chromosome 1, COL17A1 on chromosome 10, KRT10 on chromosome 17, LGALS7B on chromosome 19 and FERMT1 on chromosome 20 (Supplementary Table S8). All of these genes are involved in epithelium development and in particular with extracellular matrix (ECM) secretion and cell-ECM interactions.…”

Section: Cancer-risk Snps Regulate Cancer-related Biological Functionsmentioning

confidence: 94%

Nongenic cancer-risk SNPs affect oncogenes, tumour-suppressor genes, and immune function

et al. 2019

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BACKGROUND: Genome-wide association studies (GWASes) have identified many noncoding germline single-nucleotide polymorphisms (SNPs) that are associated with an increased risk of developing cancer. However, how these SNPs affect cancer risk is still largely unknown. METHODS: We used a systems biology approach to analyse the regulatory role of cancer-risk SNPs in thirteen tissues. By using data from the Genotype-Tissue Expression (GTEx) project, we performed an expression quantitative trait locus (eQTL) analysis. We represented both significant cis-and trans-eQTLs as edges in tissue-specific eQTL bipartite networks. RESULTS: Each tissue-specific eQTL network is organised into communities that group sets of SNPs and functionally related genes. When mapping cancer-risk SNPs to these networks, we find that in each tissue, these SNPs are significantly overrepresented in communities enriched for immune response processes, as well as tissue-specific functions. Moreover, cancer-risk SNPs are more likely to be 'cores' of their communities, influencing the expression of many genes within the same biological processes. Finally, cancer-risk SNPs preferentially target oncogenes and tumour-suppressor genes, suggesting that they may alter the expression of these key cancer genes. CONCLUSIONS: This approach provides a new way of understanding genetic effects on cancer risk and provides a biological context for interpreting the results of GWAS cancer studies.

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Section: Cancer-risk Snps Regulate Cancer-related Biological Functionsmentioning

confidence: 94%

Nongenic cancer-risk SNPs affect oncogenes, tumour-suppressor genes, and immune function

et al. 2019

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“…Then, the signal was amplified and visualized with diaminobenzidine-chromogen, followed by counterstaining with hematoxylin. TLR4, inflammation cytokines and ECM protein immunostaining were analyzed using intensity and distribution measurements as previously described (55,56) and the staining intensity was determined as follows: 0, no staining; 1, weak; 2, moderate and 3, strong. The staining distribution was determined as the percentage of positive cells (0, none; 1, <25%; 2, 25-75%; and 3, 75-100%).…”

Section: Genementioning

confidence: 99%

Overexpression of miR-140-5p inhibits lipopolysaccharide-induced human intervertebral disc inflammation and degeneration by downregulating toll-like receptor 4

et al. 2018

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Toll-like receptor 4 (TLR4) families are receptors for ligands that initiate extracellular or intracellular signaling, such as lipopolysaccharides (LPS). It has been reported that TLR4 activation resulted in the upregulation of a coordinated set of proinflammatory mediators and inhibition of matrix expression in the intervertebral disc (IVD). miR-140-5p (miR-140) is reported to participate in cellular anti-inflammatory processes and target TLR4. In the present study, we investigated the relationship between TLR4 and miR-140 in IVD degeneration. The expression of TLR4, interleukin (IL)-6, IL-I, L-1β and tumor necrosis factor (TNF)-α was higher, in high-grade IVD degeneration tissues than in low-grade tissues. In contrast, the expression of miR-140, aggrecan and collagen type II was lower in high-grade IVD degeneration tissues than in low-grade IVD degeneration tissues. LPS stimulation resulted in significant increases in TLR4 expression and decreases in miR-140 expression in nucleus pulposus (NP) cells and TLR4 was identified as a target of miR-140 by dual-luciferase reporter assay. The overexpression of miR-140 inhibited the upregulation of the expression of TLR4, TNF-α, IL-1β and IL-6 inflammation cytokines, and the activation of NF-κB and reversed the downregulation of the expression of aggrecan and collagen type II induced by LPS stimulation. In conclusion, the present study may lead to a greater understanding of IVD degeneration and provide new insights into the treatment of this disease.

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“…The signal was amplified and visualized with diaminobenzidine-chromogen, followed by counterstaining with hematoxylin. Nampt immunostaining was analyzed using intensity and distribution measurements as previously described [47][48][49]. The staining intensity was scored as 0 (no staining), 1 (weak), 2 (moderate), and 3 (strong).…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Nicotinamide Phosphoribosyltransferase Inhibitor APO866 Prevents IL-1β-Induced Human Nucleus Pulposus Cell Degeneration via Autophagy

Shi

et al. 2018

Cell Physiol Biochem

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Background/Aims: Intervertebral discs consist of an extracellular matrix (ECM) with a central gelatinous nucleus pulposus (NP) enclosed in an outer layer known as the annulus fibrosus. ECM metabolic disorders result in loss of boundary between the annulus fibrosus and NP, which can lead to intervertebral disc degeneration (IDD). Proinflammatory cytokines, such as interleukin (IL)-1β, mediate the progression of IDD. Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the first step in the biosynthesis of nicotinamide adenine dinucleotide (NAD) and is known to be induced by IL-1β. APO866 is an inhibitor of NAD biosynthesis and is involved in autophagy. LC3 (microtubule-associated protein 1 light chain 3) is a key regulator of autophagy and is used as an indicator of increased autophagy. Herein, we investigate the role of APO866 in regulating autophagy in NP cells and IL-1β mediated NP cell degeneration and apoptosis. Methods: NP cells were extracted from IDD tissues and cultured in DMEM/F12 medium. Nampt was induced by different concentrations of IL-1β (0, 0.5, 1, 5, 10 ng/mL) for 24 h or NP cells were treated with 10 ng/mL IL-1β for 0, 6, 12, 48 h. QRT-PCR and western blots were used to detect Nampt and ECM-related protein expression in NP tissue of patients with IDD and in NP cells. Confocal analysis was used to detect membrane-bound LC3, Aggrecan, and Collagen II. Results: Nampt is expressed in NP tissue at higher levels in severe grades of IDD (Grade IV and V) compared with low grades (Grade II and III). In NP cells, 10 ng/mL IL-1β induced Nampt expression for 48 h, increased expression of the degradative-associated proteins, ADAMTS4/5 and MMP-3/13, and decreased expression of ECM-related proteins, Aggrecan and Collagen II. However, the Nampt inhibitor APO866 blocked IL-1β induction, and the knockdown of Nampt expression increased the expression of ECM proteins that were inhibited by IL-1β. Moreover, evidence provided by the autophagic markers LC3 and Beclin-1 indicated that APO866 induced NP cell autophagy. Furthermore, although APO866 inhibited the downregulated expression of ECM-related proteins by IL-1β, this function was blocked by autophagy inhibitor, 3-methyladenine. Conclusion: APO866 protects NP cells and induces autophagy by inhibiting IL-1β-induced NP cell degeneration and apoptosis, which may have therapeutic potential in IDD.

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High Expression of PHGDH Predicts Poor Prognosis in Non–Small Cell Lung Cancer

Cited by 64 publications

References 34 publications

Nongenic cancer-risk SNPs affect oncogenes, tumour-suppressor genes, and immune function

Nongenic cancer-risk SNPs affect oncogenes, tumour-suppressor genes, and immune function

Overexpression of miR-140-5p inhibits lipopolysaccharide-induced human intervertebral disc inflammation and degeneration by downregulating toll-like receptor 4

Nicotinamide Phosphoribosyltransferase Inhibitor APO866 Prevents IL-1β-Induced Human Nucleus Pulposus Cell Degeneration via Autophagy

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