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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.
據(jù)報(bào)道，淋巴管生成在甲狀腺癌（THCA）的轉(zhuǎn)移中發(fā)揮著至關(guān)重要的作用，但盡管對(duì)THCA中的淋巴管生成進(jìn)行了大量研究，但其精確的調(diào)節(jié)機(jī)制仍不清楚。包括癌癥基因組圖譜（TCGA）、TIMER和UALCAN在內(nèi)的公共數(shù)據(jù)庫用于分析和可視化THCA中TET3和AHR的表達(dá)，并且TIMER使用這些分子之間的相關(guān)性。此外，還進(jìn)行RT-PCR和Western Blot來測(cè)定相關(guān)蛋白的mRNA和蛋白表達(dá)。采用平板集落形成、傷口愈合、細(xì)胞周期、凋亡、血管生成和Transwell實(shí)驗(yàn)檢測(cè)THCA細(xì)胞的增殖、運(yùn)動(dòng)、淋巴管生成、遷移和侵襲能力。TCGA 數(shù)據(jù)庫分析顯示，THCA 中腫瘤組織中 TET3 和 AHR 的表達(dá)水平高于正常組織。此外，TET3 和 AHR 之間觀察到很強(qiáng)的相關(guān)性。UALCAN 數(shù)據(jù)庫證明 TET3 和 AHR 的高表達(dá)與 THCA 患者的晚期 THCA TNM 分期相關(guān)。此外，TET3 激活通過誘導(dǎo) G2/M 期阻滯和抑制細(xì)胞凋亡來加速 THCA 細(xì)胞增殖，而 AHR 失活通過減少 G2/M 期阻滯并促進(jìn)體外細(xì)胞凋亡來減少 THCA 細(xì)胞增殖。值得注意的是，TET3 和 AHR 均顯著增強(qiáng) THCA 細(xì)胞淋巴管生成、遷移和侵襲。此外，TET3激活和AHR失活調(diào)節(jié)HIF-1α/VEGF信號(hào)通路，最終阻斷THCA細(xì)胞中的HIF-1α/VEGF并損害其運(yùn)動(dòng)、遷移和侵襲能力。TET3和AHR聯(lián)合作用通過HIF-1α/VEGF信號(hào)通路促進(jìn)THCA淋巴管生成，并靶向它們可能為THCA提供潛在的治療策略。
