The transcription factor TSHZ3 promotes tumor immunosuppression and inhibits metastasis in lung adenocarcinoma
Teashirt zinc finger homeobox 3 (TSHZ3) is a transcription factor implicated in the progression of certain cancers. However, its expression and function in lung adenocarcinoma (LUAD) remain unclear. Therefore, we aimed to investigate TSHZ3 expression and assess its prognostic significance in LUAD pa...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1519815/full |
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| author | Xi Zhang Xi Zhang Yan Liu Yan Liu Bai-Zhao Peng Xing-hong Zhou Yan-ting You Ying Yang Shuai Ji Tian-yu Zhong Xiao-hu Chen Yan-yan Liu Xiao-shan Zhao |
| author_facet | Xi Zhang Xi Zhang Yan Liu Yan Liu Bai-Zhao Peng Xing-hong Zhou Yan-ting You Ying Yang Shuai Ji Tian-yu Zhong Xiao-hu Chen Yan-yan Liu Xiao-shan Zhao |
| author_sort | Xi Zhang |
| collection | DOAJ |
| description | Teashirt zinc finger homeobox 3 (TSHZ3) is a transcription factor implicated in the progression of certain cancers. However, its expression and function in lung adenocarcinoma (LUAD) remain unclear. Therefore, we aimed to investigate TSHZ3 expression and assess its prognostic significance in LUAD patients. First, we explored prognostic data and predicted the function of TSHZ3 in lung cancer through bioinformatics analysis. We then validated the functions using cellular and animal experiments. Our results indicated that TSHZ3 expression was significantly lower in LUAD compared to normal lung tissues. High TSHZ3 expression was positively associated with better overall survival in LUAD patients. GO and pathway analyses suggested that TSHZ3 is involved in immune responses and various cancer-related processes. Immune infiltration analysis revealed correlations between TSHZ3 and immune cell infiltration, particularly macrophages, as well as the expression of numerous immune stimulators, chemokines, and receptors. Our experiment results suggest that TSHZ3 overexpression inhibits cell migration, invasion, and epithelial–mesenchymal transition (EMT) in vivo and in vitro. LUAD cells overexpressing TSHZ3 were more prone to apoptosis due to the recruitment of CD86+ macrophages. In addition, CCL2 expression was significantly higher in LUAD cells overexpressing TSHZ3, while CCR2 expression was also significantly upregulated in co-cultured macrophages. These findings suggest that TSHZ3 is an important tumor suppressor by inhibiting EMT and metastasis while inducing apoptosis through M1 macrophage chemotaxis via the CCL2/CCR2. |
| format | Article |
| id | doaj-art-bede326248f246ce84b6b235d846d2ae |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-bede326248f246ce84b6b235d846d2ae2025-08-20T02:08:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15198151519815The transcription factor TSHZ3 promotes tumor immunosuppression and inhibits metastasis in lung adenocarcinomaXi Zhang0Xi Zhang1Yan Liu2Yan Liu3Bai-Zhao Peng4Xing-hong Zhou5Yan-ting You6Ying Yang7Shuai Ji8Tian-yu Zhong9Xiao-hu Chen10Yan-yan Liu11Xiao-shan Zhao12Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, ChinaSchool of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, ChinaSchool of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, ChinaThe Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaSchool of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, ChinaSchool of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, ChinaSchool of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, ChinaSchool of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, ChinaSchool of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, ChinaSchool of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, ChinaSchool of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, ChinaSchool of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, ChinaSchool of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, ChinaTeashirt zinc finger homeobox 3 (TSHZ3) is a transcription factor implicated in the progression of certain cancers. However, its expression and function in lung adenocarcinoma (LUAD) remain unclear. Therefore, we aimed to investigate TSHZ3 expression and assess its prognostic significance in LUAD patients. First, we explored prognostic data and predicted the function of TSHZ3 in lung cancer through bioinformatics analysis. We then validated the functions using cellular and animal experiments. Our results indicated that TSHZ3 expression was significantly lower in LUAD compared to normal lung tissues. High TSHZ3 expression was positively associated with better overall survival in LUAD patients. GO and pathway analyses suggested that TSHZ3 is involved in immune responses and various cancer-related processes. Immune infiltration analysis revealed correlations between TSHZ3 and immune cell infiltration, particularly macrophages, as well as the expression of numerous immune stimulators, chemokines, and receptors. Our experiment results suggest that TSHZ3 overexpression inhibits cell migration, invasion, and epithelial–mesenchymal transition (EMT) in vivo and in vitro. LUAD cells overexpressing TSHZ3 were more prone to apoptosis due to the recruitment of CD86+ macrophages. In addition, CCL2 expression was significantly higher in LUAD cells overexpressing TSHZ3, while CCR2 expression was also significantly upregulated in co-cultured macrophages. These findings suggest that TSHZ3 is an important tumor suppressor by inhibiting EMT and metastasis while inducing apoptosis through M1 macrophage chemotaxis via the CCL2/CCR2.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1519815/fullTeashirt zinc finger homeobox 3tumor immunityapoptosislung adenocarcinomametastasisepithelial-mesenchymal transition |
| spellingShingle | Xi Zhang Xi Zhang Yan Liu Yan Liu Bai-Zhao Peng Xing-hong Zhou Yan-ting You Ying Yang Shuai Ji Tian-yu Zhong Xiao-hu Chen Yan-yan Liu Xiao-shan Zhao The transcription factor TSHZ3 promotes tumor immunosuppression and inhibits metastasis in lung adenocarcinoma Frontiers in Immunology Teashirt zinc finger homeobox 3 tumor immunity apoptosis lung adenocarcinoma metastasis epithelial-mesenchymal transition |
| title | The transcription factor TSHZ3 promotes tumor immunosuppression and inhibits metastasis in lung adenocarcinoma |
| title_full | The transcription factor TSHZ3 promotes tumor immunosuppression and inhibits metastasis in lung adenocarcinoma |
| title_fullStr | The transcription factor TSHZ3 promotes tumor immunosuppression and inhibits metastasis in lung adenocarcinoma |
| title_full_unstemmed | The transcription factor TSHZ3 promotes tumor immunosuppression and inhibits metastasis in lung adenocarcinoma |
| title_short | The transcription factor TSHZ3 promotes tumor immunosuppression and inhibits metastasis in lung adenocarcinoma |
| title_sort | transcription factor tshz3 promotes tumor immunosuppression and inhibits metastasis in lung adenocarcinoma |
| topic | Teashirt zinc finger homeobox 3 tumor immunity apoptosis lung adenocarcinoma metastasis epithelial-mesenchymal transition |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1519815/full |
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