LDHA induces EMT gene transcription and regulates autophagy to promote the metastasis and tumorigenesis of papillary thyroid carcinoma

Xiukun Hou; Xianle Shi; Wei Zhang; Dapeng Li; Linfei Hu; Jihong Yang; Jingzhu Zhao; Songfeng Wei; Xi Wei; Xianhui Ruan; Xiangqian Zheng; Ming Gao

doi:10.1038/s41419-021-03641-8

journal article Open Access Apr 01, 2021

LDHA induces EMT gene transcription and regulates autophagy to promote the metastasis and tumorigenesis of papillary thyroid carcinoma

Xiukun Hou Xianle Shi Wei Zhang

Dapeng Li

Linfei Hu Jihong Yang

Jingzhu Zhao Songfeng Wei Xi Wei

Xianhui Ruan

Xiangqian Zheng

Ming Gao

Cell Death & Disease Vol. 12 No. 4 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/s41419-021-03641-8

Abstract

AbstractPapillary 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.

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Details

Published: Apr 01, 2021
Vol/Issue: 12(4)
License: View

Authors

Hebei Agricultural University

Chinese Academy of Forestry

Funding

National Natural Science Foundation of China Award: 81872169

Natural Science Foundation of Tianjin Municipal Science and Technology Commission Award: 19JCYBJC27400

Cite This Article

Xiukun Hou, Xianle Shi, Wei Zhang, et al. (2021). LDHA induces EMT gene transcription and regulates autophagy to promote the metastasis and tumorigenesis of papillary thyroid carcinoma. Cell Death & Disease, 12(4). https://doi.org/10.1038/s41419-021-03641-8

LDHA induces EMT gene transcription and regulates autophagy to promote the metastasis and tumorigenesis of papillary thyroid carcinoma

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