DNA sensors, crucial receptors to resist pathogens, are deregulated in colorectal cancer and associated with initiation and progression of the disease
DNA sensors, crucial receptors to resist pathogens, are deregulated in colorectal cancer and associated with initiation and progression of the disease
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DOI：
10.7150/jca.34188
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发表时间：
2020-01-01
影响因子：
3.9
通讯作者：
Liu, Zhiping
中科院分区：
文献类型：
--
作者：
He, Liangmei;Liu, Yuxia;Liu, Zhiping
背景：DNA传感器是检测细胞内内源性或外源性DNA的先天性免疫受体。它们对于触发针对DNA病毒和细胞内细菌感染的免疫反应至关重要，并参与炎症性疾病和肿瘤发生。近年来越来越多的证据表明，DNA传感器在控制结直肠癌（CRC）的发展中也起着至关重要的作用。方法：利用大肠癌临床标本、小鼠AOM/DSS治疗模型和Oncomine（R）生物信息学平台，对大肠癌中DNA传感器的表达谱及其临床意义进行研究。结果：我们的研究确定了DNA传感器，包括AIM 2、DAI以及炎性体分子ASC/IL-18、TLR 9和衔接子MyD 88和DDX 60的表达在人CRC中降低，而DHX 9、DHX 36、DDX 41显著升高。其中AIM 2/ASC/IL-18、MyD 88、DAI、DHX 36、DDX 60的表达与肿瘤分期有关。此外，我们还进行了DNA传感器与其主要信号分子之间的相关性分析，以探讨其可能的机制。结果表明，AIM 2与ASC/IL-18、DHX 9与MAVS、TLR 9与MyD 88表达呈正相关。结论：多个DNA传感器在结直肠癌组织中表达失调，可能与肿瘤的发生发展有关。更重要的是，该研究发现，在所有这些DNA传感器中，AIM 2、DAI和DDX 60可能对CRC的诊断、预后和治疗至关重要，值得进一步研究。
Background: DNA sensors are innate immune receptors that detect intracellular endogenous or exogenous DNA. They are critical to trigger immune response against DNA viral and intracellular bacterial infection, and are involved in inflammatory diseases and tumorigenesis. Recent accumulating evidences indicated that DNA sensors are also crucial for controlling the development of colorectal cancer (CRC). However, a systematic study on the expression profile of DNA sensors in CRC and their clinical significance are still lacking.Methods: We investigated the expression profile of DNA sensors in CRC and their clinical significance by taking advantage of clinical CRC samples, mouse AOM/DSS treatment model, and Oncomine (R) bioinformatics platform.Results: Our study identified that the expression of DNA sensors, including AIM2, DAI, as well as inflammasome molecules ASC/IL-18, TLR9 and adaptor MyD88, and DDX60 decreased in human CRC, whereas the expression of DHX9, DHX36, and DDX41 significantly increased. Among them, the expression of AIM2/ASC/IL-18, MyD88, DAI, DHX36, and DDX60 were associated with cancer stages. In addition, we also performed correlation analysis between DNA sensors and their main signaling molecules to explore the possible mechanisms. The results showed that there were positive correlations between AIM2 and ASC/IL-1 8, DHX9 and MAVS, and TLR9 and MyD88 expression. In addition, the gene expression patterns of some DNA sensors were confirmed by Western-blot analysis.Conclusions: Our study revealed that the expression of multiple DNA sensors was deregulated in CRC and might be involved in tumor development. More importantly, the study identified that, among all these DNA sensors, AIM2, DAI, and DDX60 could be potentially critical for diagnosis, prognosis, and therapy of CRC and deserve further investigation.