Moura Edilson Leite de, Santos Israel Faustino Dos, Freitas Paulo Pedro de, Silva Denise Macedo da, Santos Ana Caroline Melo Dos, Lira Neto Abel Barbosa, Silva Aline Cristine Pereira E, Barbosa Nirliane Ribeiro, Nascimento Cristiane Araújo, Balliano Tatiane Luciano, Fraga Carlos Alberto de Carvalho, Farias Karol Fireman de, Figueiredo Elaine Virginia Martins de Souza
Laboratory of Molecular Biology and Gene Expression (LABMEG), Federal University of Alagoas (UFAL), Arapiraca, Brazil; Post-graduation Program in Health Science, Institute of Biological Sciences and Health (ICBS), Federal University of Alagoas (UFAL), Maceió, Brazil.
Laboratory of Molecular Biology and Gene Expression (LABMEG), Federal University of Alagoas (UFAL), Arapiraca, Brazil.
Immunobiology. 2022 Mar;227(2):152187. doi: 10.1016/j.imbio.2022.152187. Epub 2022 Feb 7.
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.
Toll样受体（TLR）基因多态性与宫颈癌有关，但研究结果存在一些不一致之处。本研究旨在通过荟萃分析和生物信息学分析，探讨TLR基因多态性在宫颈癌中的作用。检索了截至2020年11月的PubMed、Science Direct、Scopus和Web of science在线数据库。对于生物信息学分析，我们使用了SNP2TFBS、Raptor-X、MUpro、基因表达谱交互式分析（GEPIA）。荟萃分析结果显示，+1196T（rs4986791 TLR4）、+7764T（rs1927911 TLR4）、-1486C（rs187084 TRL9）、+2848A（rs352140 TRL9）等位基因携带者以及-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）多态性似乎会改变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IL-1β、IL-18和TNF-α的表达显著升高。这些发现表明，TLR4和TLR9基因的多态性可影响细胞内信号传导，从而改变免疫反应模式，导致宫颈癌风险增加。
