STAT3/LINC00671 axis regulates papillary thyroid tumor growth and metastasis via LDHA-mediated glycolysis
Abstract Lactate dehydrogenase A (LDHA), a critical component of the glycolytic pathway, relates to the development of various cancers, including thyroid cancer. However, the regulatory mechanism of LDHA inhibition and the physiological significance of the LDHA inhibitors in papillary thyroid cancer...
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2021-08-01
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Series: | Cell Death and Disease |
Online Access: | https://doi.org/10.1038/s41419-021-04081-0 |
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doaj-0a55de72db7b48a4b5078d40f4b7ae142021-08-22T11:07:07ZengNature Publishing GroupCell Death and Disease2041-48892021-08-0112911310.1038/s41419-021-04081-0STAT3/LINC00671 axis regulates papillary thyroid tumor growth and metastasis via LDHA-mediated glycolysisNan Huo0Rui Cong1Zhi-jia Sun2Wen-chao Li3Xiang Zhu4Chun-yuan Xue5Zhao Chen6Lu-yuan Ma7Zhong Chu8Yu-chen Han9Xiao-feng Kang10Song-hao Jia11Nan Du12Lei Kang13Xiao-jie Xu14Department of Genetic Engineering, Beijing Institute of BiotechnologyDepartment of Genetic Engineering, Beijing Institute of BiotechnologyDepartment of Oncology, Fourth Medical Center of PLA General HospitalDepartment of Paediatric Orthopaedic Surgery, Seventh Medical Center of PLA General HospitalDepartment of Genetic Engineering, Beijing Institute of BiotechnologyDepartment of Genetic Engineering, Beijing Institute of BiotechnologyDepartment of Nuclear Medicine, Peking University First HospitalDepartment of Genetic Engineering, Beijing Institute of BiotechnologyDepartment of Genetic Engineering, Beijing Institute of BiotechnologyDepartment of Genetic Engineering, Beijing Institute of BiotechnologyDepartment of Genetic Engineering, Beijing Institute of BiotechnologyDepartment of Genetic Engineering, Beijing Institute of BiotechnologyDepartment of Oncology, Fourth Medical Center of PLA General HospitalDepartment of Nuclear Medicine, Peking University First HospitalDepartment of Genetic Engineering, Beijing Institute of BiotechnologyAbstract Lactate dehydrogenase A (LDHA), a critical component of the glycolytic pathway, relates to the development of various cancers, including thyroid cancer. However, the regulatory mechanism of LDHA inhibition and the physiological significance of the LDHA inhibitors in papillary thyroid cancer (PTC) are unknown. Long non-coding RNA (lncRNA) plays a vital role in tumor growth and progression. Here, we identified a novel lncRNA LINC00671 negatively correlated with LDHA, downregulating LDHA expression and predicting good clinical outcome in thyroid cancer. Moreover, hypoxia inhibits LINC00671 expression and activates LDHA expression largely through transcriptional factor STAT3. STAT3/LINC00671/LDHA axis regulates thyroid cancer glycolysis, growth, and lung metastasis both in vitro and in vivo. In thyroid cancer patients, LINC00671 expression is negatively correlated with LDHA and STAT3 expression. Our work established STAT3/LINC00671/LDHA as a critical axis to regulate PTC growth and progression. Inhibition of LDHA or STAT3 or supplement of LINC00671 could be potential therapeutic strategies in thyroid cancer.https://doi.org/10.1038/s41419-021-04081-0 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nan Huo Rui Cong Zhi-jia Sun Wen-chao Li Xiang Zhu Chun-yuan Xue Zhao Chen Lu-yuan Ma Zhong Chu Yu-chen Han Xiao-feng Kang Song-hao Jia Nan Du Lei Kang Xiao-jie Xu |
spellingShingle |
Nan Huo Rui Cong Zhi-jia Sun Wen-chao Li Xiang Zhu Chun-yuan Xue Zhao Chen Lu-yuan Ma Zhong Chu Yu-chen Han Xiao-feng Kang Song-hao Jia Nan Du Lei Kang Xiao-jie Xu STAT3/LINC00671 axis regulates papillary thyroid tumor growth and metastasis via LDHA-mediated glycolysis Cell Death and Disease |
author_facet |
Nan Huo Rui Cong Zhi-jia Sun Wen-chao Li Xiang Zhu Chun-yuan Xue Zhao Chen Lu-yuan Ma Zhong Chu Yu-chen Han Xiao-feng Kang Song-hao Jia Nan Du Lei Kang Xiao-jie Xu |
author_sort |
Nan Huo |
title |
STAT3/LINC00671 axis regulates papillary thyroid tumor growth and metastasis via LDHA-mediated glycolysis |
title_short |
STAT3/LINC00671 axis regulates papillary thyroid tumor growth and metastasis via LDHA-mediated glycolysis |
title_full |
STAT3/LINC00671 axis regulates papillary thyroid tumor growth and metastasis via LDHA-mediated glycolysis |
title_fullStr |
STAT3/LINC00671 axis regulates papillary thyroid tumor growth and metastasis via LDHA-mediated glycolysis |
title_full_unstemmed |
STAT3/LINC00671 axis regulates papillary thyroid tumor growth and metastasis via LDHA-mediated glycolysis |
title_sort |
stat3/linc00671 axis regulates papillary thyroid tumor growth and metastasis via ldha-mediated glycolysis |
publisher |
Nature Publishing Group |
series |
Cell Death and Disease |
issn |
2041-4889 |
publishDate |
2021-08-01 |
description |
Abstract Lactate dehydrogenase A (LDHA), a critical component of the glycolytic pathway, relates to the development of various cancers, including thyroid cancer. However, the regulatory mechanism of LDHA inhibition and the physiological significance of the LDHA inhibitors in papillary thyroid cancer (PTC) are unknown. Long non-coding RNA (lncRNA) plays a vital role in tumor growth and progression. Here, we identified a novel lncRNA LINC00671 negatively correlated with LDHA, downregulating LDHA expression and predicting good clinical outcome in thyroid cancer. Moreover, hypoxia inhibits LINC00671 expression and activates LDHA expression largely through transcriptional factor STAT3. STAT3/LINC00671/LDHA axis regulates thyroid cancer glycolysis, growth, and lung metastasis both in vitro and in vivo. In thyroid cancer patients, LINC00671 expression is negatively correlated with LDHA and STAT3 expression. Our work established STAT3/LINC00671/LDHA as a critical axis to regulate PTC growth and progression. Inhibition of LDHA or STAT3 or supplement of LINC00671 could be potential therapeutic strategies in thyroid cancer. |
url |
https://doi.org/10.1038/s41419-021-04081-0 |
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