LDHA induces EMT gene transcription and regulates autophagy to promote the metastasis and tumorigenesis of papillary thyroid carcinoma
Abstract Papillary thyroid carcinoma (PTC) is one of the most common kinds of endocrine-related cancer and has a heterogeneous prognosis. Metabolic reprogramming is one of the hallmarks of cancers. Aberrant glucose metabolism is associated with malignant biological behavior. However, the functions a...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-04-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-03641-8 |
| _version_ | 1818566618185203712 |
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| author | Xiukun Hou Xianle Shi Wei Zhang Dapeng Li Linfei Hu Jihong Yang Jingzhu Zhao Songfeng Wei Xi Wei Xianhui Ruan Xiangqian Zheng Ming Gao |
| author_facet | Xiukun Hou Xianle Shi Wei Zhang Dapeng Li Linfei Hu Jihong Yang Jingzhu Zhao Songfeng Wei Xi Wei Xianhui Ruan Xiangqian Zheng Ming Gao |
| author_sort | Xiukun Hou |
| collection | DOAJ |
| description | Abstract Papillary thyroid carcinoma (PTC) is one of the most common kinds of endocrine-related cancer and has a heterogeneous prognosis. Metabolic reprogramming is one of the hallmarks of cancers. Aberrant glucose metabolism is associated with malignant biological behavior. However, the functions and mechanisms of glucose metabolism genes in PTC are not fully understood. Thus, data from The Cancer Genome Atlas database were analyzed, and lactate dehydrogenase A (LDHA) was determined to be a potential novel diagnostic and therapeutic target for PTCs. The research objective was to investigate the expression of LDHA in PTCs and to explore the main functions and relative mechanisms of LDHA in PTCs. Higher expression levels of LDHA were found in PTC tissues than in normal thyroid tissues at both the mRNA and protein levels. Higher expression levels of LDHA were correlated with aggressive clinicopathological features and poor prognosis. Moreover, we found that LDHA not only promoted PTC migration and invasion but also enhanced tumor growth both in vitro and in vivo. In addition, we revealed that the metabolic products of LDHA catalyzed induced the epithelial–mesenchymal transition process by increasing the relative gene H3K27 acetylation. Moreover, LDHA knockdown activated the AMPK pathway and induced protective autophagy. An autophagy inhibitor significantly enhanced the antitumor effect of FX11. These results suggested that LDHA enhanced the cell metastasis and proliferation of PTCs and may therefore become a potential therapeutic target for PTCs. |
| first_indexed | 2024-12-14T01:56:03Z |
| format | Article |
| id | doaj.art-408a7957434547a6892ba9f593efb0d2 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-14T01:56:03Z |
| publishDate | 2021-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-408a7957434547a6892ba9f593efb0d22022-12-21T23:21:11ZengNature Publishing GroupCell Death and Disease2041-48892021-04-0112411810.1038/s41419-021-03641-8LDHA induces EMT gene transcription and regulates autophagy to promote the metastasis and tumorigenesis of papillary thyroid carcinomaXiukun Hou0Xianle Shi1Wei Zhang2Dapeng Li3Linfei Hu4Jihong Yang5Jingzhu Zhao6Songfeng Wei7Xi Wei8Xianhui Ruan9Xiangqian Zheng10Ming Gao11Department of Thyroid and Neck Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerDepartment of Medicine, Columbia Center for Human Development, Columbia University Irving Medical CenterDepartment of Thyroid and Neck Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerDepartment of Thyroid and Neck Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerDepartment of Thyroid and Neck Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerDepartment of Medicine, Columbia Center for Human Development, Columbia University Irving Medical CenterDepartment of Thyroid and Neck Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerDepartment of Thyroid and Neck Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerDepartment of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerDepartment of Thyroid and Neck Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerDepartment of Thyroid and Neck Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerDepartment of Thyroid and Neck Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerAbstract Papillary thyroid carcinoma (PTC) is one of the most common kinds of endocrine-related cancer and has a heterogeneous prognosis. Metabolic reprogramming is one of the hallmarks of cancers. Aberrant glucose metabolism is associated with malignant biological behavior. However, the functions and mechanisms of glucose metabolism genes in PTC are not fully understood. Thus, data from The Cancer Genome Atlas database were analyzed, and lactate dehydrogenase A (LDHA) was determined to be a potential novel diagnostic and therapeutic target for PTCs. The research objective was to investigate the expression of LDHA in PTCs and to explore the main functions and relative mechanisms of LDHA in PTCs. Higher expression levels of LDHA were found in PTC tissues than in normal thyroid tissues at both the mRNA and protein levels. Higher expression levels of LDHA were correlated with aggressive clinicopathological features and poor prognosis. Moreover, we found that LDHA not only promoted PTC migration and invasion but also enhanced tumor growth both in vitro and in vivo. In addition, we revealed that the metabolic products of LDHA catalyzed induced the epithelial–mesenchymal transition process by increasing the relative gene H3K27 acetylation. Moreover, LDHA knockdown activated the AMPK pathway and induced protective autophagy. An autophagy inhibitor significantly enhanced the antitumor effect of FX11. These results suggested that LDHA enhanced the cell metastasis and proliferation of PTCs and may therefore become a potential therapeutic target for PTCs.https://doi.org/10.1038/s41419-021-03641-8 |
| spellingShingle | Xiukun Hou Xianle Shi Wei Zhang Dapeng Li Linfei Hu Jihong Yang Jingzhu Zhao Songfeng Wei Xi Wei Xianhui Ruan Xiangqian Zheng Ming Gao LDHA induces EMT gene transcription and regulates autophagy to promote the metastasis and tumorigenesis of papillary thyroid carcinoma Cell Death and Disease |
| title | LDHA induces EMT gene transcription and regulates autophagy to promote the metastasis and tumorigenesis of papillary thyroid carcinoma |
| title_full | LDHA induces EMT gene transcription and regulates autophagy to promote the metastasis and tumorigenesis of papillary thyroid carcinoma |
| title_fullStr | LDHA induces EMT gene transcription and regulates autophagy to promote the metastasis and tumorigenesis of papillary thyroid carcinoma |
| title_full_unstemmed | LDHA induces EMT gene transcription and regulates autophagy to promote the metastasis and tumorigenesis of papillary thyroid carcinoma |
| title_short | LDHA induces EMT gene transcription and regulates autophagy to promote the metastasis and tumorigenesis of papillary thyroid carcinoma |
| title_sort | ldha induces emt gene transcription and regulates autophagy to promote the metastasis and tumorigenesis of papillary thyroid carcinoma |
| url | https://doi.org/10.1038/s41419-021-03641-8 |
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