Leucine-rich glioma inactivated 3 and tumor necrosis factor-α regulate mutually through NF-κB

Kim, Hyun A; Kwon, Nyoun Soo; Baek, Kwang Jin; Kim, Dong-Seok; Yun, Hye‐Young

doi:10.1016/j.cyto.2014.12.023

Cited by 11 publications

(43 citation statements)

References 15 publications

(35 reference statements)

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“…Abundant expression and its functional elucidation including LGI3-regulated genes were reported in neuronal cells, adipocytes, macrophages, keratinocytes and melanocytes 3–5,9. Our finding that the expressions of LGI3 and its receptors were positively associated with the prognosis of glioma (Figure 3) suggested that LGI3 may play a role as a suppressor of glioma progression through its receptor-mediated mechanisms.…”

Section: Discussionmentioning

confidence: 73%

“…LGI protein members were shown to be differentially expressed in various types of tumor cells (glioma, neuroblastoma, melanoma, colon and breast cancers), and LGI3 was the only LGI family member expressed at significant levels in glioma, melanoma and neuroblastoma 11. This study was prompted by our previous reports supporting the roles of LGI3 as a multifunctional cytokine4–9 and the predicted association of LGI3 with cytokine network in cancer 18…”

Section: Discussionmentioning

confidence: 91%

“…Our previous studies identified 48 gene products that were regulated by LGI3 1–9,18. LGI3 was postulated to participate in cytokine network through regulating various cytokines and secreted factors including TNF-α, adiponectin, C–C motif chemokine ligand 2 (CCL2, MCP-1), C-X-C motif chemokine ligand 13 (CXCL13), C-X-C motif chemokine ligand 2 (CXCL2), C-reactive protein (CRP), TIMP1, colony-stimulating factor 1 (CSF1), CSF3, complement C5 (C5), endothelial cell-specific molecule 1 (ESM1), IGF1, insulin-like growth factor-binding protein 1 (IGFBP1), IGFBP5, interleukin 6 (IL6), lipoprotein lipase (LPL) and SERPINE1 18.…”

Section: Discussionmentioning

confidence: 99%

“…Our finding that the expressions of LGI3 and its receptors were positively associated with the prognosis of glioma (Figure 3) suggested that LGI3 may play a role as a suppressor of glioma progression through its receptor-mediated mechanisms. LGI3 was reported to transduce intracellular signals through proteins crucially involved in cancers including ADAM23, Akt, β-catenin, focal adhesion kinase, MDM2, p53, NF-κB and microphthalmia-associated transcription factor (MITF) 3,5,6,9,35–38. Perturbation of these proteins by downregulated LGI3 and its receptors in glioma may account for the role of LGI3 in pathogenesis and prognosis in glioma and other cancers 18.…”

Section: Discussionmentioning

confidence: 99%

“…LGI3 downregulated the anti-inflammatory adipokine, adiponectin 8. LGI3 and TNF-α upregulated each other through NF-κB in preadipocytes, suggesting their cooperative involvement in metabolic inflammation in obesity 9. We proposed that LGI3 is a multifunctional cytokine and adipokine released by and acting at various cell types and that LGI3 may be a proinflammatory cytokine that interplayed with multiple cytokines.…”

Section: Introductionmentioning

confidence: 95%

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Leucine-rich glioma inactivated 3: integrative analyses support its prognostic role in glioma

Kwon¹,

Kim²,

Yun³

2017

OTT

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BackgroundLeucine-rich glioma inactivated 3 (LGI3) is a secreted protein member of LGI family. We previously reported that LGI3 was expressed in brain, adipose tissues and skin, where it played roles as a multifunctional cytokine. We postulated that LGI3 may be involved in cytokine network in cancers.AimThis study aimed to analyze differentially expressed genes in glioma tissues and glioma cohort data to investigate the prognostic role of LGI3 and its receptors.Materials and methodsExpression microarray data from Gene Expression Omnibus and glioma cohort data were analyzed using bioinformatic tools for statistical analysis, protein–protein interactions, functional enrichment and pathway analyses and prognostic association analysis.ResultsWe found that LGI3 and its receptors, ADAM22 and ADAM23, were significantly downregulated in glioma tissues. Eleven upregulated genes and two downregulated genes in glioma tissues were found to be the previously reported LGI3-regulated genes. Protein–protein interaction network analysis showed that 85% of the LGI3-regulated and glioma-altered genes formed a cluster of interaction network. Functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed the association of these genes with hypoxia responses, p53 and Akt signaling and various cancer-related pathways including glioma. Analysis of expression microarray data of glioma cohorts demonstrated that low expression levels of LGI3, ADAM22 and ADAM23 were significantly associated with poor prognosis of glioma.ConclusionThese results propose that LGI3 and its receptors may play a prognostic role in glioma.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

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Leucine-rich glioma inactivated 3: integrative analyses support its prognostic role in glioma

Kwon¹,

Kim²,

Yun³

2017

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Bromodomain-containing protein 2 induces insulin resistance via the mTOR/Akt signaling pathway and an inflammatory response in adipose tissue

Sun

Hou

et al. 2017

Cellular Signalling

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Leucine rich repeat LGI family member 3: Integrative analyses support its prognostic association with pancreatic adenocarcinoma

Yun

2024

Medicine

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Leucine rich repeat LGI family member 3 (LGI3) is a member of the LGI protein family. Previous studies of our group have reported that LGI3 is expressed in adipose tissue, skin and brain, and serves as a multifunctional cytokine. LGI3 may also be involved in cytokine networks in various cancers. This study aimed to analyze differentially expressed genes in pancreatic adenocarcinoma (PAC) tissues and PAC cohort data in order to evaluate the prognostic role of LGI3. The expression microarray and the PAC cohort data were analyzed by bioinformatic methods for differential expression, protein-protein interactions, functional enrichment and pathway analyses, gene co-expression network analysis, and prognostic association analysis. Results showed that LGI3 expression was significantly reduced in PAC tissues. Nineteen upregulated genes and 31 downregulated genes in PAC tissues were identified as LGI3-regulated genes. Protein-protein interaction network analysis demonstrated that 92% (46/50) of the LGI3-regulated genes that were altered in PACs belonged to a protein-protein interaction network cluster. Functional enrichment and gene co-expression network analyses demonstrated that these genes in the network cluster were associated with various processes including inflammatory and immune responses, metabolic processes, cell differentiation, and angiogenesis. PAC cohort analyses revealed that low expression levels of LGI3 were significantly associated with poor PAC prognosis. Analysis of favorable or unfavorable prognostic gene products in PAC showed that 93 LGI3-regulated genes were differentially associated with PAC prognosis. LGI3 expression was correlated with the tumor-infiltration levels of various immune cells. Taken together, these results suggested that LGI3 may be a potential prognostic marker of PAC.

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Leucine-rich glioma inactivated 3 and tumor necrosis factor-α regulate mutually through NF-κB

Cited by 11 publications

References 15 publications

Leucine-rich glioma inactivated 3: integrative analyses support its prognostic role in glioma

Leucine-rich glioma inactivated 3: integrative analyses support its prognostic role in glioma

Bromodomain-containing protein 2 induces insulin resistance via the mTOR/Akt signaling pathway and an inflammatory response in adipose tissue

Leucine rich repeat LGI family member 3: Integrative analyses support its prognostic association with pancreatic adenocarcinoma

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