LDHA induces EMT gene transcription and regulates autophagy to promote the metastasis and tumorigenesis of papillary thyroid carcinoma.
LDHA induces EMT gene transcription and regulates autophagy to promote the metastasis and tumorigenesis of papillary thyroid carcinoma.
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LDHA诱导EMT基因转录并调节自噬促进甲状腺乳头状癌的转移和致瘤
DOI：
10.1038/s41419-021-03641-8
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发表时间：
2021-04-01
影响因子：
9
通讯作者：
Gao M
中科院分区：
文献类型：
--
作者：
Hou X;Shi X;Zhang W;Li D;Hu L;Yang J;Zhao J;Wei S;Wei X;Ruan X;Zheng X;Gao M
甲状腺乳头状癌（PTC）是一种最常见的内分泌相关性癌症，预后不一。代谢重编程是癌症的标志之一。糖代谢异常与恶性生物学行为有关。然而，葡萄糖代谢基因在PTC中的功能和机制尚不完全清楚。因此，分析了来自癌症基因组图谱数据库的数据，并确定乳酸脱氢酶A（LDHA）是PTC的潜在新诊断和治疗靶点。研究LDHA在PTCs中的表达，探讨LDHA在PTCs中的主要作用及相关机制。LDHA在PTC组织中的表达水平高于正常甲状腺组织。LDHA的高表达水平与临床病理特征的侵袭性和预后不良相关。此外，我们发现LDHA不仅促进PTC迁移和侵袭，而且在体外和体内都促进肿瘤生长。此外，我们发现LDHA的代谢产物通过增加相关基因H3 K27的乙酰化来催化诱导上皮-间充质转化过程。此外，LDHA敲低激活AMPK通路并诱导保护性自噬。自噬抑制剂显著增强FX 11的抗肿瘤作用。这些结果表明，LDHA促进了PTC的细胞转移和增殖，因此可能成为PTC的潜在治疗靶点。
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.
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影响因子：
29
作者：
Pavlova NN;Thompson CB
通讯作者：
Thompson CB
DOI：
10.1073/pnas.0914433107
发表时间：
2010-02-02
影响因子：
11.1
作者：
Le, Anne;Cooper, Charles R.;Dang, Chi V.
通讯作者：
Dang, Chi V.
DOI：
10.1038/nrc.2017.53
发表时间：
2017-09
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Levy JMM;Towers CG;Thorburn A
通讯作者：
Thorburn A
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
5.9
作者：
Lee P;Vousden KH;Cheung EC
通讯作者：
Cheung EC