文章摘要：Lymphangiogenesis has been reported to play crucial roles in the metastasis of thyroid cancer (THCA), but despite the significant research on lymphangiogenesis in THCA, the precise regulatory mechanism remains unclear. Public databases including the Cancer Genome Atlas (TCGA), TIMER, and UALCAN were used to analyze and visualize the expression of TET3 and AHR in THCA, and the correlation between these molecules were used by TIMER. Additionally, RT-PCR and Western Blot were performed to determine the mRNA and protein expression of related proteins. Plate colony formation, wound healing, cell cycle, apoptosis, angiogenesis and transwell assay were used to examine the ability of proliferation, movement, lymphangiogenesis, migration and invasion of THCA cells. Analysis of the TCGA database revealed higher expression levels of TET3 and AHR in tumor tissue compared to normal tissue in THCA. Additionally, a strong correlation was observed between TET3 and AHR. UALCAN database demonstrated that high expression of TET3 and AHR was associated with advanced THCA TNM stages in THCA patients. Furthermore, TET3 activation accelerated THCA cell proliferation by inducing G2/M phase arrest and suppressing apoptosis, while AHR inactivation reduced THCA cell proliferation by decreasing G2/M phase arrest and promoting apoptosis in vitro. Notably, both TET3 and AHR significantly enhanced THCA cell lymphangiogenesis, migration and invasion. Moreover, TET3 activation and AHR inactivation regulated HIF-1α/VEGF signaling pathway, which ultimately, blocked the HIF-1α/VEGF in THCA cells and impaired their movement, migration and invasion abilities. The combined action of TET3 and AHR to promote lymphangiogenesis in THCA through the HIF-1α/VEGF signaling pathway, and targeting them might provide a potential treatment strategy for THCA.

据报道，淋巴管生成在甲状腺癌（THCA）的转移中发挥着至关重要的作用，但尽管对THCA中的淋巴管生成进行了大量研究，但其精确的调节机制仍不清楚。包括癌症基因组图谱（TCGA）、TIMER和UALCAN在内的公共数据库用于分析和可视化THCA中TET3和AHR的表达，并且TIMER使用这些分子之间的相关性。此外，还进行RT-PCR和Western Blot来测定相关蛋白的mRNA和蛋白表达。采用平板集落形成、伤口愈合、细胞周期、凋亡、血管生成和Transwell实验检测THCA细胞的增殖、运动、淋巴管生成、迁移和侵袭能力。TCGA 数据库分析显示，THCA 中肿瘤组织中 TET3 和 AHR 的表达水平高于正常组织。此外，TET3 和 AHR 之间观察到很强的相关性。UALCAN 数据库证明 TET3 和 AHR 的高表达与 THCA 患者的晚期 THCA TNM 分期相关。此外，TET3 激活通过诱导 G2/M 期阻滞和抑制细胞凋亡来加速 THCA 细胞增殖，而 AHR 失活通过减少 G2/M 期阻滞并促进体外细胞凋亡来减少 THCA 细胞增殖。值得注意的是，TET3 和 AHR 均显着增强 THCA 细胞淋巴管生成、迁移和侵袭。此外，TET3激活和AHR失活调节HIF-1α/VEGF信号通路，最终阻断THCA细胞中的HIF-1α/VEGF并损害其运动、迁移和侵袭能力。TET3和AHR联合作用通过HIF-1α/VEGF信号通路促进THCA淋巴管生成，并靶向它们可能为THCA提供潜在的治疗策略。