The novel oncogenic factor TET3 combines with AHR to promote thyroid cancer lymphangiogenesis via the HIF-1α/VEGF signaling pathway
Abstract Background 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. Methods Public databases including the Cancer Genome Atlas (T...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-023-03021-6 |
| _version_ | 1797451430277152768 |
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| author | Liyun Yang Runyu Zhao Peipei Qiao Jiaxin Cui Xiaoping Chen Jinping Fan An Hu Shuixian Huang |
| author_facet | Liyun Yang Runyu Zhao Peipei Qiao Jiaxin Cui Xiaoping Chen Jinping Fan An Hu Shuixian Huang |
| author_sort | Liyun Yang |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions 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. |
| first_indexed | 2024-03-09T14:54:33Z |
| format | Article |
| id | doaj.art-c6bba96e4bab49a3a9ec4992ff053bb4 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-03-09T14:54:33Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-c6bba96e4bab49a3a9ec4992ff053bb42023-11-26T14:18:15ZengBMCCancer Cell International1475-28672023-09-0123111410.1186/s12935-023-03021-6The novel oncogenic factor TET3 combines with AHR to promote thyroid cancer lymphangiogenesis via the HIF-1α/VEGF signaling pathwayLiyun Yang0Runyu Zhao1Peipei Qiao2Jiaxin Cui3Xiaoping Chen4Jinping Fan5An Hu6Shuixian Huang7Department of Otolaryngology Head and Neck Surgery, Gongli Hospital, the Second Military Medical UniversityPostgraduate Training Base at Shanghai Gongli Hospital, Ningxia Medical UniversityPostgraduate Training Base at Shanghai Gongli Hospital, Ningxia Medical UniversityDepartment of Otolaryngology Head and Neck Surgery, Gongli Hospital, the Second Military Medical UniversityDepartment of Otolaryngology Head and Neck Surgery, Gongli Hospital, the Second Military Medical UniversityDepartment of Otolaryngology Head and Neck Surgery, Changzheng Hospital, the Second Military Medical UniversityDepartment of Otolaryngology Head and Neck Surgery, Gongli Hospital, the Second Military Medical UniversityDepartment of Otolaryngology Head and Neck Surgery, Gongli Hospital, the Second Military Medical UniversityAbstract Background 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. Methods 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. Results 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. Conclusions 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.https://doi.org/10.1186/s12935-023-03021-6Thyroid cancerLymphangiogenesisTET3AHRHIF-1α/VEGF signaling pathway |
| spellingShingle | Liyun Yang Runyu Zhao Peipei Qiao Jiaxin Cui Xiaoping Chen Jinping Fan An Hu Shuixian Huang The novel oncogenic factor TET3 combines with AHR to promote thyroid cancer lymphangiogenesis via the HIF-1α/VEGF signaling pathway Cancer Cell International Thyroid cancer Lymphangiogenesis TET3 AHR HIF-1α/VEGF signaling pathway |
| title | The novel oncogenic factor TET3 combines with AHR to promote thyroid cancer lymphangiogenesis via the HIF-1α/VEGF signaling pathway |
| title_full | The novel oncogenic factor TET3 combines with AHR to promote thyroid cancer lymphangiogenesis via the HIF-1α/VEGF signaling pathway |
| title_fullStr | The novel oncogenic factor TET3 combines with AHR to promote thyroid cancer lymphangiogenesis via the HIF-1α/VEGF signaling pathway |
| title_full_unstemmed | The novel oncogenic factor TET3 combines with AHR to promote thyroid cancer lymphangiogenesis via the HIF-1α/VEGF signaling pathway |
| title_short | The novel oncogenic factor TET3 combines with AHR to promote thyroid cancer lymphangiogenesis via the HIF-1α/VEGF signaling pathway |
| title_sort | novel oncogenic factor tet3 combines with ahr to promote thyroid cancer lymphangiogenesis via the hif 1α vegf signaling pathway |
| topic | Thyroid cancer Lymphangiogenesis TET3 AHR HIF-1α/VEGF signaling pathway |
| url | https://doi.org/10.1186/s12935-023-03021-6 |
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