The production of cytokines in response to DNA-damage events may be an important host defense response to help prevent the escape of pre-cancerous cells. The innate immune pathways involved in these events are known to be regulated by cellular molecules such as stimulator of interferon genes (STING), which controls type I interferon and pro-inflammatory cytokine production in response to the presence of microbial DNA or cytosolic DNA that has escaped from the nucleus. STING signaling has been shown to be defective in a variety of cancers, such as colon cancer and melanoma, actions that may enable damaged cells to escape the immunosurveillance system. Here, we report through examination of databases that STING signaling may be commonly suppressed in a greater variety of tumors due to loss-of-function mutation or epigenetic silencing of the STING/cGAS promoter regions. In comparison, RNA activated innate immune pathways controlled by RIG-I/MDA5 were significantly less affected. Examination of reported missense STING variants confirmed that many exhibited a loss-of-function phenotype and could not activate cytokine production following exposure to cytosolic DNA or DNA-damage events. Our data imply that the STING signaling pathway may be recurrently suppressed by a number of mechanisms in a considerable variety of malignant disease and be a requirement for cellular transformation.

中文翻译：

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通过表观遗传沉默和错义突变抑制STING信号传导会阻止DNA损伤介导的细胞因子产生。

响应DNA损伤事件的细胞因子的产生可能是重要的宿主防御反应，有助于防止癌前细胞逃逸。已知与这些事件有关的先天免疫途径受细胞分子（例如干扰素基因刺激剂（STING）的调节）的调节，这些分子可响应微生物DNA或胞浆DNA的存在而控制I型干扰素和促炎性细胞因子的产生。从核中逃脱了。已经显示出STING信号传导在多种癌症中是缺陷的，例如结肠癌和黑素瘤，这些作用可使受损细胞逃脱免疫监视系统。这里，我们通过数据库检查报告，由于功能缺失突变或STING / cGAS启动子区域的表观遗传沉默，在更多种类的肿瘤中通常可能抑制STING信号传导。相比之下，由RIG-I / MDA5控制的RNA激活的先天免疫途径受到的影响要小得多。对报告的错义STING变体的检查证实，许多暴露于胞质DNA或DNA损伤事件后，它们表现出功能丧失的表型，并且不能激活细胞因子的产生。我们的数据表明，在相当多的恶性疾病中，STING信号通路可能会被多种机制反复抑制，这是细胞转化的必要条件。受RIG-I / MDA5控制的RNA激活的先天性免疫途径受到的影响明显较小。对报告的错义STING变体的检查证实，许多暴露于胞质DNA或DNA损伤事件后，它们表现出功能丧失的表型，并且不能激活细胞因子的产生。我们的数据表明，在相当多的恶性疾病中，STING信号通路可能会被多种机制反复抑制，这是细胞转化的必要条件。受RIG-I / MDA5控制的RNA激活的先天性免疫途径受到的影响明显较小。对报告的错义STING变体的检查证实，许多暴露于胞质DNA或DNA损伤事件后，它们表现出功能丧失的表型，并且不能激活细胞因子的产生。我们的数据表明，在相当多的恶性疾病中，STING信号通路可能会被多种机制反复抑制，这是细胞转化的必要条件。