CAJ | 학술논문

目的探讨人脑胶质母细胞瘤中核因子-κB抑制因子α(NFKBIA)蛋白水平及其与NFKBIA mRNA表达水平、变异、拷贝数变异的关系.方法收集24例胶质母细胞瘤组织标本,应用聚合酶链反应(PCR)扩增及直接测序检测NFKBIA变异,Western blot检测NFKBIA蛋白表达,实时定量PCR检测NFKBIA拷贝数变异及mRNA表达.结果胶质母细胞瘤中存在NFKIBA单核苷酸多态性rs1957106 (CC/CT/TF);胶质母细胞瘤中NFKBIA蛋白表达量在CT基因型和TT基因型显著低于CC基因型:CT和TT:(10.1±1.2)％、CC:(40.1±2.8)％;胶质母细胞瘤中NFKBIA蛋白表达量和NFKBIA mRNA表达水平均显著低于非瘤组织:肿瘤组织中NFKBIA的相对表达分别为:(28.2±12.5)％、(0.44±0.19),非瘤组织中NFKBIA的相对表达分别为:(64.3±1.7)％、(0.78±0.12);而且含有CT基因型和TT基因型的胶质母细胞瘤NFKBIA mRNA表达水平明显低于含有CC基因型的胶质母细胞瘤:CT和TT:0.31±0.11,CC:0.54 ±0.18;P＜0.01;含有CT基因型或TT基因型的10个胶质母细胞瘤中有7个的拷贝数显著低于含有CC基因型的肿瘤,而这些胶质母细胞瘤同时有低NFKBIA蛋白及低NFKBIA mRNA表达水平.结论 NFKBIA单核苷酸多态性rs 1957106与NFKBIA低蛋白表达、低拷贝数密切相关.
목적 탐토인뇌효질모세포류중핵인자-κB억제인자α(NFKBIA)단백수평급기여NFKBIA mRNA표체수평、변이、고패수변이적관계.방법 수집24례효질모세포류조직표본,응용취합매련반응(PCR)확증급직접측서검측NFKBIA변이,Western blot검측NFKBIA단백표체,실시정량PCR검측NFKBIA고패수변이급mRNA표체.결과 효질모세포류중존재NFKIBA단핵감산다태성rs1957106 (CC/CT/TF);효질모세포류중NFKBIA단백표체량재CT기인형화TT기인형현저저우CC기인형:CT화TT:(10.1±1.2)％、CC:(40.1±2.8)％;효질모세포류중NFKBIA단백표체량화NFKBIA mRNA표체수평균현저저우비류조직:종류조직중NFKBIA적상대표체분별위:(28.2±12.5)％、(0.44±0.19),비류조직중NFKBIA적상대표체분별위:(64.3±1.7)％、(0.78±0.12);이차함유CT기인형화TT기인형적효질모세포류NFKBIA mRNA표체수평명현저우함유CC기인형적효질모세포류:CT화TT:0.31±0.11,CC:0.54 ±0.18;P＜0.01;함유CT기인형혹TT기인형적10개효질모세포류중유7개적고패수현저저우함유CC기인형적종류,이저사효질모세포류동시유저NFKBIA단백급저NFKBIA mRNA표체수평.결론 NFKBIA단핵감산다태성rs 1957106여NFKBIA저단백표체、저고패수밀절상관.
Objective The aim of the present study was to explore nuclear factor-κB inhibitor-α (NFKBIA) protein levels and their relationship with mRNA levels,mutation and copy number variation of NFKBIA in glioblastomas.This will lay a foundation for further clarifying the role of NFKBIA in the development of glioblastomas.Methods We analyzed 24 human glioblastoma samples and 8 samples of noncancerous brain tissue for mutations,copy number variation and expression (protein and mRNA levels) of NFKBIA.We used polymerase chain reaction(PCR) amplification and direct sequencing to detect mutaions of NFKBIA,Western blotting to detect expression of NFKBIA protein,real-time quantitative PCR to detect copy number variation and mRNA expression of NFKBIA.Results We genotyped one single nucleotide polymorphism rs1957106 in NFKBIA in glioblastomas.NFKBIA protein levels detected were significantly lower in glioblastomas harboring the rs1957106 CT and TT genotypes than in samples harboring the rs1957106 CC genotype:CT and TT:(10.1 ± 1.2)％,CC:(40.1 ±2.8)％.Moreover,NFKBIA protein levels were significantly lower in glioblastomas than in non-cancerous brain tissues:tumor:(28.2 ± 12.5) ％,non-cancerous brain tissue:(64.3 ± 1.7) ％.NFKBIA mRNA levels were lower in glioblastomas compared with non-cancerous brain tissue,tumor:0.44 ±0.19,non-cancerous brain tissue:0.78 ± 0.12.Furthermore,NFKBIA mRNA levels were significantly lower in glioblastomas harboring the rs1957106 CT and TT genotypes than in samples harboring the rs1957106 CC genotype (CT and TT:0.31 ± 0.11,CC:0.54 ± 0.18),P ＜ 0.01.The relative copy number of NFKBIA was significantly lower in 7 of the 10 glioblastomas,all of which had the rs1957106 CT and TT genotypes and low NFKBIA protein levels.Conclusion The minor allele for one synonymous single nucleotide polymorphism in NFKBIA,rs1957106,was associated with lower protein expression and lower copy number of NFKBIA.