Toll样受体基因的多态性改变宿主的免疫反应并与宫颈癌有关,Immunobiology

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Toll样受体基因的多态性改变宿主的免疫反应并与宫颈癌有关
Immunobiology ( IF 2.5 ) Pub Date : 2022-02-07 , DOI: 10.1016/j.imbio.2022.152187
Edilson Leite de Moura ₁ , Israel Faustino Dos Santos ₂ , Paulo Pedro de Freitas ₂ , Denise Macedo da Silva ₁ , Ana Caroline Melo Dos Santos ₁ , Abel Barbosa Lira Neto ₂ , Aline Cristine Pereira E Silva ₂ , Nirliane Ribeiro Barbosa ₂ , Cristiane Araújo Nascimento ₂ , Tatiane Luciano Balliano ₃ , Carlos Alberto de Carvalho Fraga ₄ , Karol Fireman de Farias ₂ , Elaine Virginia Martins de Souza Figueiredo ₁

Affiliation

Toll 样受体 ( TLR ) 基因的多态性与宫颈癌有关，但在结果中发现了一些不一致之处。本研究旨在通过荟萃分析和生物信息学分析研究TLRs基因多态性在宫颈癌中的作用。在 PubMed、Science Direct、Scopus 和 Web of science 在线数据库中进行搜索，直到 2020 年 11 月。对于生物信息学分析，我们使用了 SNP2TFBS、Raptor-X、MUpro、基因表达谱交互分析 (GEPIA)。Meta分析结果显示+1196T（rs4986791 TLR4）、+7764T（rs1927911 TLR4）、-1486C（rs187084 TRL9）+2848A（rs352140 TRL9) 等位基因携带者和 -2604G/G (rs10759931 TLR4 )、-1237C/C (rs5743836 TRL9 ) 基因型与宫颈癌风险增加相关。生物信息学分析表明，-1237T>C（rs5743836）和-1486T>C（rs187084）多态性可以影响TLR9基因中的转录因子结合位点（RELA、NFKB1和THAP1），+2848G>A（rs352140）多态性似乎改变了 TLR4 蛋白的结构和稳定性。此外，使用 GEPIA 观察到，与正常组织相比，宫颈癌组织中的 IL-1β、IL-18 和 TNF-α 表达显着升高。这些发现表明TLR4和TLR9中的多态性基因可以影响细胞内信号传导，从而改变免疫反应的模式，从而增加患宫颈癌的风险。

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Polymorphisms in Toll-like receptors genes changes the host’s immune response and is associated with cervical cancer

Polymorphisms in Toll-like receptors (TLRs) genes have been associated with cervical cancer, but some inconsistencies were found in the results. The present study aimed to investigate the role of polymorphisms in the TLRs genes in cervical cancer, through meta-analysis and bioinformatics analysis. Searches were performed in PubMed, Science Direct, Scopus and Web of science online databases until November 2020. For bioinformatics analysis, we used SNP2TFBS, Raptor-X, MUpro, Gene Expression Profiling Interactive Analysis (GEPIA). The results of meta-analysis showed that the +1196T (rs4986791 TLR4), +7764T (rs1927911 TLR4), -1486C (rs187084 TRL9) +2848A (rs352140 TRL9) alleles carriers and -2604G/G (rs10759931 TLR4), -1237C/C (rs5743836 TRL9) genotypes were associated with an increased risk for cervical cancer. The bioinformatics analysis revealed that the -1237T>C (rs5743836) and -1486T>C (rs187084) polymorphisms can affect the transcription factors binding sites (RELA, NFKB1 and THAP1) in the TLR9 gene, and the +2848G>A (rs352140) polymorphism seems to alter the structure and stability of TLR4 protein. Additionally, using GEPIA, was observed a significantly high of IL-1β, IL-18 and TNF-α expression in cervical cancer tissues compared to normal tissues. These finds indicate that polymorphisms in the TLR4 and TLR9 genes can affect intracellular signaling and, consequently, change the patterns of the immune response, leading to an increased risk for cervical cancer.

更新日期：2022-02-07

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