肺腺癌（LUAD）的准确诊断、治疗和预后的新分子方法的有效鉴定与开发仍然是一项迫切的临床需求。基因组中的胞嘧啶碱基的DNA甲基化模式与基因表达密切相关，各种癌症中经常观察到异常的DNA甲基化。十一转座（TET）酶氧化5-甲基胞嘧啶（5mC）并促进位点特异性DNA甲基化逆转。本研究旨在探讨TET2蛋白及其下游效应物5-羟甲基胞嘧啶（5-hmC）/5-甲基胞嘧啶（5-mC）DNA修饰在LUAD进展中的作用。通过实时PCR、Western blot和免疫组织化学分析TET2的表达。使用比色试剂盒确定5-hmC DNA含量。通过Western blot评估cGAS-STING信号通路的活化情况。进行CCK-8、伤口愈合和Transwell实验评估TET2对细胞增殖、迁移和侵袭能力的影响。使用异种移植模型分析TET2对A549细胞的肿瘤能力的影响。TET2过表达可抑制体外和体内A549和H1975细胞的增殖和转移。然而，TET2敲低显著增强了A549和H1975细胞的增殖，迁移和侵袭能力。机制上，cGAS-STING信号通路的活化对于TET2介导的LUAD细胞的肿瘤发生和转移抑制至关重要。本研究证明了TET2在LUAD中的抑癌作用，为非小细胞肺癌患者提供了新的潜在分子治疗靶点和临床治疗策略。© 2023. BioMed Central Ltd., part of Springer Nature.

Effective identification and development of new molecular methods for the diagnosis, treatment and prognosis of lung adenocarcinoma (LUAD) remains an urgent clinical need. DNA methylation patterns at cytosine bases in the genome are closely related to gene expression, and abnormal DNA methylation is frequently observed in various cancers. The ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (5mC) and promote locus-specific DNA methylation reversal. This study aimed to explore the role of the TET2 protein and its downstream effector, 5-hmC/5-mC DNA modification, in LUAD progression.The expression of TET2 was analysed by real-time PCR, Western blotting and immunohistochemistry. The 5-hmC DNA content was determined by a colorimetric kit. Activation of the cGAS-STING signalling pathway was evaluated by Western blotting. CCK-8, wound healing and Transwell assays were performed to evaluate the effect of TET2 on cell proliferation, migration and invasion abilities. A xenograft model was used to analyse the effect of TET2 on the tumorigenic ability of A549 cells.TET2 overexpression decreased proliferation and metastasis of A549 and H1975 cells in vitro and in vivo. However, TET2 knockdown dramatically enhanced the proliferation, migration and invasion of A549 and H1975 cells. Mechanistically, activation of the cGAS-STING signalling pathway is critical for the TET2-mediated suppression of LUAD cell tumorigenesis and metastasis.In this study, we demonstrate a tumour suppressor role of TET2 in LUAD, providing new potential molecular therapeutic targets and clinical therapies for patients with non-small cell lung cancer.© 2023. BioMed Central Ltd., part of Springer Nature.