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Identification of a NFKBIA polymorphism associated with lower NFKBIA protein levels and poor survival outcomes in patients with glioblastoma multiforme.

Zhao Z, Zhong X, Wu T, Yang T, Chen G, Xie X, Wei Y, Ye M, Zhou Y, Du Z - Int. J. Mol. Med. (2014)

Bottom Line: The aberrant constitutive activation of nuclear factor-κB (NF-κB) has been observed in glioblastomas, while NF-κB inhibitor alpha (NFKBIA) inhibits the NF-κB signaling pathway under several physiological processes.In the present study, using gene sequencing, we identified rs1957106 as a novel single nucleotide polymorphism (SNP) in NFKBIA in glioblastoma and found that it was more frequently present in glioblastoma patients.The SNP rs1957106 CT and TT genotypes were found to be associated with lower NFKBIA protein levels and a poor prognosis of pateints with glioblastoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.

ABSTRACT
The aberrant constitutive activation of nuclear factor-κB (NF-κB) has been observed in glioblastomas, while NF-κB inhibitor alpha (NFKBIA) inhibits the NF-κB signaling pathway under several physiological processes. However, the contribution of NFKBIA to glioblastomas is poorly understood. In the present study, using gene sequencing, we identified rs1957106 as a novel single nucleotide polymorphism (SNP) in NFKBIA in glioblastoma and found that it was more frequently present in glioblastoma patients. In addition, we examined the association between different genotypes of the rs1957106 SNP of NFKBIA and the gene copy number, mRNA level and protein expression of NFKBIA. The SNP rs1957106 CT and TT genotypes were found to be associated with lower NFKBIA protein levels and a poor prognosis of pateints with glioblastoma. Hence, by identifying rs1957106 as a novel SNP in NFKBIA in glioblastoma patients, we provide a new platform for further investigating the function of NFKBIA in the pathobiology of glioblastoma.

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Related in: MedlinePlus

Relative expression levels of nuclear factor-κB inhibitor alpha (NFKBIA). mRNA expression measured by RT-qPCR. NFKBIA mRNA levels were lower in all genotypes of SNP rs1957106 in NFKBIA in glioblastomas compared with non-cancerous brain tissue. Furthermore, NFKBIA mRNA levels were significantly lower in glioblastomas harboring the single nucleotide polymorphism (SNP) rs1957106 CT and TT genotypes than in those harboring the SNP rs1957106 CC genotype. Data are presented based on the 2−ΔΔCT method. P-values were calculated using one way analysis of variance, with the Student-Newman-Keuls (SNK) post hoc test. ***P≤0.001.
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f4-ijmm-34-05-1233: Relative expression levels of nuclear factor-κB inhibitor alpha (NFKBIA). mRNA expression measured by RT-qPCR. NFKBIA mRNA levels were lower in all genotypes of SNP rs1957106 in NFKBIA in glioblastomas compared with non-cancerous brain tissue. Furthermore, NFKBIA mRNA levels were significantly lower in glioblastomas harboring the single nucleotide polymorphism (SNP) rs1957106 CT and TT genotypes than in those harboring the SNP rs1957106 CC genotype. Data are presented based on the 2−ΔΔCT method. P-values were calculated using one way analysis of variance, with the Student-Newman-Keuls (SNK) post hoc test. ***P≤0.001.

Mentions: We performed qPCR to examine whether there were significant differences in the mRNA expression of NFKBIA in glioblastomas compared with non-cancerous brain tissue samples and in glioblastomas harboring different genotypes of SNP rs1957106. As shown in Fig. 4, the NFKBIA mRNA levels were lower in the glioblastoma compared with the non-cancerous brain tissue samples. Furthermore, the NFKBIA mRNA levels were significantly lower in the glioblastomas harboring the SNP rs1957106 CT and TT genotypes than in the samples harboring the SNP rs1957106 CC genotype (CT/TT 0.31±0.11 vs. CC 0.54±0.18 vs. non-cancerous 0.78±0.12, P<0.001). These data suggest that the lower protein expression levels of NFKBIA are in accordance with the lower mRNA expression levels of NFKBIA in glioblastomas.


Identification of a NFKBIA polymorphism associated with lower NFKBIA protein levels and poor survival outcomes in patients with glioblastoma multiforme.

Zhao Z, Zhong X, Wu T, Yang T, Chen G, Xie X, Wei Y, Ye M, Zhou Y, Du Z - Int. J. Mol. Med. (2014)

Relative expression levels of nuclear factor-κB inhibitor alpha (NFKBIA). mRNA expression measured by RT-qPCR. NFKBIA mRNA levels were lower in all genotypes of SNP rs1957106 in NFKBIA in glioblastomas compared with non-cancerous brain tissue. Furthermore, NFKBIA mRNA levels were significantly lower in glioblastomas harboring the single nucleotide polymorphism (SNP) rs1957106 CT and TT genotypes than in those harboring the SNP rs1957106 CC genotype. Data are presented based on the 2−ΔΔCT method. P-values were calculated using one way analysis of variance, with the Student-Newman-Keuls (SNK) post hoc test. ***P≤0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4199416&req=5

f4-ijmm-34-05-1233: Relative expression levels of nuclear factor-κB inhibitor alpha (NFKBIA). mRNA expression measured by RT-qPCR. NFKBIA mRNA levels were lower in all genotypes of SNP rs1957106 in NFKBIA in glioblastomas compared with non-cancerous brain tissue. Furthermore, NFKBIA mRNA levels were significantly lower in glioblastomas harboring the single nucleotide polymorphism (SNP) rs1957106 CT and TT genotypes than in those harboring the SNP rs1957106 CC genotype. Data are presented based on the 2−ΔΔCT method. P-values were calculated using one way analysis of variance, with the Student-Newman-Keuls (SNK) post hoc test. ***P≤0.001.
Mentions: We performed qPCR to examine whether there were significant differences in the mRNA expression of NFKBIA in glioblastomas compared with non-cancerous brain tissue samples and in glioblastomas harboring different genotypes of SNP rs1957106. As shown in Fig. 4, the NFKBIA mRNA levels were lower in the glioblastoma compared with the non-cancerous brain tissue samples. Furthermore, the NFKBIA mRNA levels were significantly lower in the glioblastomas harboring the SNP rs1957106 CT and TT genotypes than in the samples harboring the SNP rs1957106 CC genotype (CT/TT 0.31±0.11 vs. CC 0.54±0.18 vs. non-cancerous 0.78±0.12, P<0.001). These data suggest that the lower protein expression levels of NFKBIA are in accordance with the lower mRNA expression levels of NFKBIA in glioblastomas.

Bottom Line: The aberrant constitutive activation of nuclear factor-κB (NF-κB) has been observed in glioblastomas, while NF-κB inhibitor alpha (NFKBIA) inhibits the NF-κB signaling pathway under several physiological processes.In the present study, using gene sequencing, we identified rs1957106 as a novel single nucleotide polymorphism (SNP) in NFKBIA in glioblastoma and found that it was more frequently present in glioblastoma patients.The SNP rs1957106 CT and TT genotypes were found to be associated with lower NFKBIA protein levels and a poor prognosis of pateints with glioblastoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.

ABSTRACT
The aberrant constitutive activation of nuclear factor-κB (NF-κB) has been observed in glioblastomas, while NF-κB inhibitor alpha (NFKBIA) inhibits the NF-κB signaling pathway under several physiological processes. However, the contribution of NFKBIA to glioblastomas is poorly understood. In the present study, using gene sequencing, we identified rs1957106 as a novel single nucleotide polymorphism (SNP) in NFKBIA in glioblastoma and found that it was more frequently present in glioblastoma patients. In addition, we examined the association between different genotypes of the rs1957106 SNP of NFKBIA and the gene copy number, mRNA level and protein expression of NFKBIA. The SNP rs1957106 CT and TT genotypes were found to be associated with lower NFKBIA protein levels and a poor prognosis of pateints with glioblastoma. Hence, by identifying rs1957106 as a novel SNP in NFKBIA in glioblastoma patients, we provide a new platform for further investigating the function of NFKBIA in the pathobiology of glioblastoma.

Show MeSH
Related in: MedlinePlus