Open Access

RelB, a good prognosis predictor, links cell-cycle and migration to glioma tumorigenesis

  • Authors:
    • Feng Shen
    • Qing Guo
    • Qi Hu
    • Ailiang Zeng
    • Weining Wu
    • Wei Yan
    • Yongping You
  • View Affiliations

  • Published online on: January 29, 2018     https://doi.org/10.3892/ol.2018.7894
  • Pages: 4404-4410
  • Copyright: © Shen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Nuclear factor κB (NF‑κB) exhibits an important role in inflammation and tumorigenesis. The key regulatory protein of the pathway, RELB Proto‑Oncogene, NF‑KB Subunit (relB), is overexpressed and associated with the pathogenesis of a variety of malignant tumors. However, the molecular features and clinical signature of relB expression in gliomas remains to be elucidated. The present study obtained the raw sequencing data of 325 glioma samples of all grades from the Chinese Glioma Genome Atlas (CGGA) database and human glioma cell line (LN229) from the Chinese Academy of Sciences cell bank. Cell proliferation, invasion and wound healing assays were used for functional annotation of relB. Western blot analysis was used for validating the protein expression of relB, matrix metalloproteinase (MMP)‑2 and MMP‑9 in a further 77 glioma samples. In Diffuse Glioma data, relB expression was associated with glioma grade, demonstrated a mesenchymal subtype preference and cell development association. The downregulation of relB expression inhibited glioma cell migration and invasion by regulating the MMPs in vitro. relB expression was independently associated with grade and prognosis of grade III and grade IV gliomas, suggesting that relB is a novel biomarker with therapeutic potential for predicting prognosis in glioma.

References

1 

Wang Y and Jiang T: Understanding high grade glioma: Molecular mechanism, therapy and comprehensive management. Cancer Lett. 331:139–146. 2013. View Article : Google Scholar : PubMed/NCBI

2 

van den Bent M, Chinot OL and Cairncross JG: Recent developments in the molecular characterization and treatment of oligodendroglial tumors. Neuro Oncol. 5:128–138. 2003. View Article : Google Scholar : PubMed/NCBI

3 

Kalpathy-Cramer J, Gerstner ER, Emblem KE, Andronesi OC and Rosen B: Advanced magnetic resonance imaging of the physical processes in human glioblastoma. Cancer Res. 74:4622–4637. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Van Schaeybroeck S, Allen WL, Turkington RC and Johnston PG: Implementing prognostic and predictive biomarkers in CRC clinical trials. Nat Rev Clin Oncol. 8:222–232. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Reis-Filho JS and Pusztai L: Gene expression profiling in breast cancer: Classification, prognostication, and prediction. Lancet. 378:1812–1823. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Hayden MS and Ghosh S: NF-κB, the first quarter-century: Remarkable progress and outstanding questions. Genes Dev. 26:203–234. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Perkins ND: The diverse and complex roles of NF-κB subunits in cancer. Nat Rev Cancer. 12:121–132. 2012. View Article : Google Scholar : PubMed/NCBI

8 

DiDonato JA, Mercurio F and Karin M: NF-κB and the link between inflammation and cancer. Immunol Rev. 246:379–400. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Cha ST, Tan CT, Chang CC, Chu CY, Lee WJ, Lin BZ, Lin MT and Kuo ML: Retraction: G9a/RelB regulates self-renewal and function of colon-cancer-initiating cells by silencing Let-7b and activating the K-RAS/β-catenin pathway. Nat Cell Biol. 19:762016. View Article : Google Scholar : PubMed/NCBI

10 

Kitamura T, Kometani K, Hashida H, Matsunaga A, Miyoshi H, Hosogi H, Aoki M, Oshima M, Hattori M, Takabayashi A, et al: SMAD4-deficient intestinal tumors recruit CCR1+ myeloid cells that promote invasion. Nat Genet. 39:467–475. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Kenagy RD, Hart CE, Stetler-Stevenson WG and Clowes AW: Primate smooth muscle cell migration from aortic explants is mediated by endogenous platelet-derived growth factor and basic fibroblast growth factor acting through matrix metalloproteinases 2 and 9. Circulation. 96:3555–3560. 1997. View Article : Google Scholar : PubMed/NCBI

12 

Ge QL, Liu SH, Ai ZH, Tao MF, Ma L, Wen SY, Dai M, Liu F, Liu HS, Jiang RZ, et al: RelB/NF-κB links cell cycle transition and apoptosis to endometrioid adenocarcinoma tumorigenesis. Cell Death Dis. 7:e24022016. View Article : Google Scholar : PubMed/NCBI

13 

Sau A, Lau R, Cabrita MA, Nolan E, Crooks PA, Visvader JE and Pratt MA: Persistent activation of NF-κB in BRCA1-deficient mammary progenitors drives aberrant proliferation and accumulation of DNA damage. Cell Stem Cell. 19:52–65. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Gardella KA, Muro I, Fang G, Sarkar K, Mendez O and Wright CW: Aryl hydrocarbon receptor nuclear translocator (ARNT) isoforms control lymphoid cancer cell proliferation through differentially regulating tumor suppressor p53 activity. Oncotarget. 7:10710–10722. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Hänzelmann S, Castelo R and Guinney J: GSVA: Gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics. 14:72013. View Article : Google Scholar : PubMed/NCBI

16 

Zheng H, Takahashi H, Murai Y, Cui Z, Nomoto K, Niwa H, Tsuneyama K and Takano Y: Expressions of MMP-2, MMP-9 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma. Anticancer Res. 26:3579–3583. 2006.PubMed/NCBI

17 

Deryugina EI and Quigley JP: Tumor angiogenesis: MMP-mediated induction of intravasation- and metastasis-sustaining neovasculature. Matrix Biol 44–46. 1–112. 2015.

18 

Gao M, Zhang X, Li D, He P, Tian W and Zeng B: Expression analysis and clinical significance of eIF4E, VEGF-C, E-cadherin and MMP-2 in colorectal adenocarcinoma. Oncotarget. 7:85502–85514. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Guo F, Tänzer S, Busslinger M and Weih F: Lack of nuclear factor-kappa B2/p100 causes a RelB-dependent block in early B lymphopoiesis. Blood. 112:551–559. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Bellet MM, Zocchi L and Sassone-Corsi P: The RelB subunit of NFκB acts as a negative regulator of circadian gene expression. Cell Cycle. 11:3304–3311. 2012. View Article : Google Scholar : PubMed/NCBI

21 

McMillan DH, Baglole CJ, Thatcher TH, Maggirwar S, Sime PJ and Phipps RP: Lung-targeted overexpression of the NF-κB member RelB inhibits cigarette smoke-induced inflammation. Am J Pathol. 179:125–133. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Xu Y, Josson S, Fang F, Oberley TD, St Clair DK, Wan XS, Sun Y, Bakthavatchalu V, Muthuswamy A and St Clair WH: RelB enhances prostate cancer growth: Implications for the role of the nuclear factor-kappaB alternative pathway in tumorigenicity. Cancer Res. 69:3267–3271. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Zhu L, Zhu B, Yang L, Zhao X, Jiang H and Ma F: RelB regulates Bcl-xl expression and the irradiation-induced apoptosis of murine prostate cancer cells. Biomed Rep. 2:354–358. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Mineva ND, Wang X, Yang S, Ying H, Xiao ZX, Holick MF and Sonenshein GE: Inhibition of RelB by 1,25-dihydroxyvitamin D3 promotes sensitivity of breast cancer cells to radiation. J Cell Physiol. 220:593–599. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Xu J, Zhou P, Sun A and Guo F: Effect of nuclear transcription factor RelB on the proteasome inhibitor-sensitivity of chronic lymphocytic leukemia cells. Zhonghua Xue Ye Xue Za Zhi. 35:524–527. 2014.(In Chinese). PubMed/NCBI

26 

Roskelley CD, Srebrow A and Bissell MJ: A hierarchy of ECM-mediated signalling regulates tissue-specific gene expression. Curr Opin Cell Biol. 7:736–747. 1995. View Article : Google Scholar : PubMed/NCBI

27 

Park HI, Ni J, Gerkema FE, Liu D, Belozerov VE and Sang QX: Identification and characterization of human endometase (Matrix metalloproteinase-26) from endometrial tumor. J Biol Chem. 275:20540–20544. 2000. View Article : Google Scholar : PubMed/NCBI

28 

Shah FD, Shukla SN, Shah PM, Shukla HK and Patel PS: Clinical significance of matrix metalloproteinase 2 and 9 in breast cancer. Indian J Cancer. 46:194–202. 2009. View Article : Google Scholar : PubMed/NCBI

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April 2018
Volume 15 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Copy and paste a formatted citation
APA
Shen, F., Guo, Q., Hu, Q., Zeng, A., Wu, W., Yan, W., & You, Y. (2018). RelB, a good prognosis predictor, links cell-cycle and migration to glioma tumorigenesis. Oncology Letters, 15, 4404-4410. https://doi.org/10.3892/ol.2018.7894
MLA
Shen, F., Guo, Q., Hu, Q., Zeng, A., Wu, W., Yan, W., You, Y."RelB, a good prognosis predictor, links cell-cycle and migration to glioma tumorigenesis". Oncology Letters 15.4 (2018): 4404-4410.
Chicago
Shen, F., Guo, Q., Hu, Q., Zeng, A., Wu, W., Yan, W., You, Y."RelB, a good prognosis predictor, links cell-cycle and migration to glioma tumorigenesis". Oncology Letters 15, no. 4 (2018): 4404-4410. https://doi.org/10.3892/ol.2018.7894