The novel oncogenic factor TET3 combined AHR to promote Thyroid cancer lymphangiogenesis via HIF-1α/VEGF signaling pathway

Abstract

Background Lymphangiogenesis is an important factor in the invasion and metastasis of thyroid cancer (THCA). The relative researches of lymphangiogenesis have always been a hot topic in THCA, but its specific regulatory mechanism has not been totally clear. Methods Public databases including the Cancer Genome Atlas (TCGA), TIMER, GEPIA, and UALCAN database were employed to analyze and visualize the expression and prognosis of TET3 and AHR in THCA. GEPIA and TIMER were used to analyze the correlation between these molecules. Rt-PCR and Western Blot were used to detect the mRNA and protein expression of related proteins. Plate colony formation, cycle, apoptosis, angiogenesis and transwell assay were used to examine the ability of proliferation, lymphangiogenesis and invasion of THCA cells. Results TCGA database were showed that TET3 and AHR in tumor tissue compared to normal tissue in THCA. And there was a high correlation between TET3 and AHR. UALCAN and GEPIA database were exhibited that high expression of TET3 and AHR were corelated with THCA TNM stages and poor prognosis of THCA patients. Moreover, the TET3 activation accelerated THCA cells proliferation by inducing G2/M phase arrest and restraining apoptosis, and the AHR inactivation reduced THCA cells proliferation by decreasing G2/M phase arrest and inducing apoptosis in vitro of THCA cells. Notably, TET3 and AHR markedly promoted THCA cells lymphangiogenesis and invasion. In addition, TET3 activation and AHR inactivation regulated HIF-1α/VEGF signaling pathway. Conclusions TET3 combined AHR to promote THCA lymphangiogenesis via HIF-1α/VEGF signaling pathway and targeting TET3 and AHR might provide a potential treatment strategy for THCA.