Lactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma

Abstract Lactate dehydrogenase A (LDHA) has been reported to be involved in the initiation and progression of tumors. However, the potential role of LDHA in pituitary adenoma (PA) remains unknown. In this study, we showed that the expression levels of LDHA mRNA and protein were significantly elevate...

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Autores principales:	Jiayin An, Yin Zhang, Jiaojiang He, Zhenle Zang, Zheng Zhou, Xiangdong Pei, Xin Zheng, Weihua Zhang, Hui Yang, Song Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e2ef473ec04142868f18cda463c5940e
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spelling	oai:doaj.org-article:e2ef473ec04142868f18cda463c5940e2021-12-02T15:04:56ZLactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma10.1038/s41598-017-04366-52045-2322https://doaj.org/article/e2ef473ec04142868f18cda463c5940e2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04366-5https://doaj.org/toc/2045-2322Abstract Lactate dehydrogenase A (LDHA) has been reported to be involved in the initiation and progression of tumors. However, the potential role of LDHA in pituitary adenoma (PA) remains unknown. In this study, we showed that the expression levels of LDHA mRNA and protein were significantly elevated in invasive PA samples, and positively correlated with higher Ki-67 index. Overexpression of LDHA in a PA cell line (GH3) promoted glucose uptake through the upregulation of glucose transporter-1 (Glut1), lactate secretion and induced cellular invasion by upregulation of matrix metalloproteinase2 (MMP2). LDHA also promoted GH3 cell proliferation through induction of cell cycle progression via activation of the Akt-GSK-3β-cyclinD1 pathway. Accordingly, oxamate-induced inhibition of LDHA suppressed glucose uptake, lactate secretion, invasion and proliferation in GH3 cells via down regulation of Glut1 and MMP2 expression and inhibition of the Akt-GSK-3β-cyclinD1 pathway. Moreover, oxamate induced GH3 cell apoptosis by increasing mitochondrial reactive oxygen species (ROS) generation. In vivo, LDHA overexpression promoted tumor growth, and oxamate delayed tumor growth. In primary PA cell cultures, oxamate also effectively suppressed invasion and proliferation. Our data indicate that LDHA is involved in promoting the progression of PA, and oxamate might be a promising therapeutic agent for the treatment of PA.Jiayin AnYin ZhangJiaojiang HeZhenle ZangZheng ZhouXiangdong PeiXin ZhengWeihua ZhangHui YangSong LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jiayin An Yin Zhang Jiaojiang He Zhenle Zang Zheng Zhou Xiangdong Pei Xin Zheng Weihua Zhang Hui Yang Song Li Lactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma
description	Abstract Lactate dehydrogenase A (LDHA) has been reported to be involved in the initiation and progression of tumors. However, the potential role of LDHA in pituitary adenoma (PA) remains unknown. In this study, we showed that the expression levels of LDHA mRNA and protein were significantly elevated in invasive PA samples, and positively correlated with higher Ki-67 index. Overexpression of LDHA in a PA cell line (GH3) promoted glucose uptake through the upregulation of glucose transporter-1 (Glut1), lactate secretion and induced cellular invasion by upregulation of matrix metalloproteinase2 (MMP2). LDHA also promoted GH3 cell proliferation through induction of cell cycle progression via activation of the Akt-GSK-3β-cyclinD1 pathway. Accordingly, oxamate-induced inhibition of LDHA suppressed glucose uptake, lactate secretion, invasion and proliferation in GH3 cells via down regulation of Glut1 and MMP2 expression and inhibition of the Akt-GSK-3β-cyclinD1 pathway. Moreover, oxamate induced GH3 cell apoptosis by increasing mitochondrial reactive oxygen species (ROS) generation. In vivo, LDHA overexpression promoted tumor growth, and oxamate delayed tumor growth. In primary PA cell cultures, oxamate also effectively suppressed invasion and proliferation. Our data indicate that LDHA is involved in promoting the progression of PA, and oxamate might be a promising therapeutic agent for the treatment of PA.
format	article
author	Jiayin An Yin Zhang Jiaojiang He Zhenle Zang Zheng Zhou Xiangdong Pei Xin Zheng Weihua Zhang Hui Yang Song Li
author_facet	Jiayin An Yin Zhang Jiaojiang He Zhenle Zang Zheng Zhou Xiangdong Pei Xin Zheng Weihua Zhang Hui Yang Song Li
author_sort	Jiayin An
title	Lactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma
title_short	Lactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma
title_full	Lactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma
title_fullStr	Lactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma
title_full_unstemmed	Lactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma
title_sort	lactate dehydrogenase a promotes the invasion and proliferation of pituitary adenoma
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e2ef473ec04142868f18cda463c5940e
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_version_	1718388989126246400

Lactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma

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