Laboratory of Microbiological Engineering and Applications, University of Constantine 1, Constantine, Algeria.
Laboratory of Computational and Functional Oncology, Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
Cancer Rep (Hoboken). 2020 Jun;3(3):e1240. doi: 10.1002/cnr2.1240. Epub 2020 Feb 20.
The link between inflammation and cancer development was intensively studied in the last decade. To date, few studies explored the association between inflammatory genes and colorectal cancer (CRC) development.
The present study aimed to evaluate the implication of three single nucleotide polymorphisms (SNPs), rs28362491 ins/del -94 ATTG in NFκB1, rs6920220 (G/A) in TNFAIP3, and rs419598 (C/T) in IL1RN, which play a role in inflammation regulation in CRC development.
A case-control study was conducted on an Algerian cohort of 358 subjects (147 healthy people, 89 individuals affected by inflammatory bowel disease [IBD], and 122 CRC patients enrolled at the University Hospital Center Ben Badis of Constantine). SNPs genotyping was performed by allelic discrimination TaqMan assay. The rs28362491 ins/del heterozygous genotype in NFκB1 conferred an increased risk of IBD compared with ins/ins homozygous genotype, with an increase of twofold (OR = 2.34 [1.29-4.21]; 95% CI, 1.29-4.21, P value = 0.004). No significant association was detected for the other two variants. Dual-Luciferase Reporter Assay System performed in LoVo cells showed a significantly higher activity of the construct with ins allele of rs28362491 compared with the one harboring the del allele. Computational analysis nominated SOX9 as putative transcription factor (TF) with higher probability to bind the NFκB1 promoter at the SNP site, and we demonstrated in the in vitro assay that its overexpression modulates NFκB1 promoter activity in allele-specific manner.
We speculate that SOX9 may modulate the NFκB1 activity by binding its promoter at the SNP site in allelic specific manner.
在过去的十年中，炎症与癌症发展之间的联系得到了深入研究。迄今为止，很少有研究探讨炎症基因与结直肠癌（CRC）发展之间的关系。
本研究旨在评估三个单核苷酸多态性（SNP），即 NFκB1 中的 rs28362491 插入/缺失-94 ATTG、TNFAIP3 中的 rs6920220（G/A）和 IL1RN 中的 rs419598（C/T）在 CRC 发展中的作用。这些 SNP 参与炎症调节。
在阿尔及利亚君士坦丁大学贝巴迪斯医院中心进行了一项病例对照研究，纳入了 358 名受试者（147 名健康人、89 名炎症性肠病[IBD]患者和 122 名 CRC 患者）。通过等位基因鉴别 TaqMan 分析进行 SNP 基因分型。与 NFκB1 中 ins/ins 纯合基因型相比，rs28362491 杂合基因型增加了 IBD 的风险，增加了两倍（OR=2.34[1.29-4.21]；95%CI，1.29-4.21，P 值=0.004）。另外两个变体没有发现显著相关性。在 LoVo 细胞中进行的双荧光素酶报告基因检测系统显示，携带 rs28362491ins 等位基因的构建体活性明显高于携带 del 等位基因的构建体。计算分析提名 SOX9 为可能的转录因子（TF），它以更高的概率在 SNP 位点结合 NFκB1 启动子，并且我们在体外实验中证明，其过表达以等位基因特异性方式调节 NFκB1 启动子活性。
我们推测 SOX9 可能通过在 SNP 位点以等位基因特异性方式结合其启动子来调节 NFκB1 的活性。
