The miR-125a/HK2 axis regulates cancer cell energy metabolism reprogramming in hepatocellular carcinoma

Abstract The Warburg effect is a metabolic hallmark of cancer. Tumor cells rapidly adjust their energy source to glycolysis in order to efficiently proliferate in a hypoxic environment, but the mechanism underlying this switch remains incompletely understood. Here, we show that hypoxia potently indu...

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Autores principales:	Fangfang Jin, Yanbo Wang, Yanan Zhu, Shan Li, Ying Liu, Cheng Chen, Xiaohua Wang, Ke Zen, Limin Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0a1c7709519d43c2ab6c9d02a8031c76
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spelling	oai:doaj.org-article:0a1c7709519d43c2ab6c9d02a8031c762021-12-02T15:05:52ZThe miR-125a/HK2 axis regulates cancer cell energy metabolism reprogramming in hepatocellular carcinoma10.1038/s41598-017-03407-32045-2322https://doaj.org/article/0a1c7709519d43c2ab6c9d02a8031c762017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03407-3https://doaj.org/toc/2045-2322Abstract The Warburg effect is a metabolic hallmark of cancer. Tumor cells rapidly adjust their energy source to glycolysis in order to efficiently proliferate in a hypoxic environment, but the mechanism underlying this switch remains incompletely understood. Here, we show that hypoxia potently induces the down-regulation of miR-125a expression in hepatocellular carcinoma (HCC) cells and tumors. Furthermore, we demonstrate that miR-125a could decrease the production of lactate, the uptake of glucose, and the levels of ATP and reactive oxygen species (ROS) in HCC cells. We investigated the molecular mechanism through which miR-125a inhibits HCC glycolysis and identified hexokinase II (HK2) as a direct target gene of miR-125a. Finally, we revealed that the miR-125a/HK2 axis is functionally important for regulating glycolysis of HCC cell and progression of cancer in vitro and in vivo. In summary, our findings demonstrate for the first time that hypoxia-down-regulated miR-125a regulated HCC glycolysis and carcinogenesis by targeting hexokinase HK2, a key glycolytic enzyme for the Warburg effect, and add a new dimension to hypoxia-mediated regulation of cancer metabolism.Fangfang JinYanbo WangYanan ZhuShan LiYing LiuCheng ChenXiaohua WangKe ZenLimin 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 Fangfang Jin Yanbo Wang Yanan Zhu Shan Li Ying Liu Cheng Chen Xiaohua Wang Ke Zen Limin Li The miR-125a/HK2 axis regulates cancer cell energy metabolism reprogramming in hepatocellular carcinoma
description	Abstract The Warburg effect is a metabolic hallmark of cancer. Tumor cells rapidly adjust their energy source to glycolysis in order to efficiently proliferate in a hypoxic environment, but the mechanism underlying this switch remains incompletely understood. Here, we show that hypoxia potently induces the down-regulation of miR-125a expression in hepatocellular carcinoma (HCC) cells and tumors. Furthermore, we demonstrate that miR-125a could decrease the production of lactate, the uptake of glucose, and the levels of ATP and reactive oxygen species (ROS) in HCC cells. We investigated the molecular mechanism through which miR-125a inhibits HCC glycolysis and identified hexokinase II (HK2) as a direct target gene of miR-125a. Finally, we revealed that the miR-125a/HK2 axis is functionally important for regulating glycolysis of HCC cell and progression of cancer in vitro and in vivo. In summary, our findings demonstrate for the first time that hypoxia-down-regulated miR-125a regulated HCC glycolysis and carcinogenesis by targeting hexokinase HK2, a key glycolytic enzyme for the Warburg effect, and add a new dimension to hypoxia-mediated regulation of cancer metabolism.
format	article
author	Fangfang Jin Yanbo Wang Yanan Zhu Shan Li Ying Liu Cheng Chen Xiaohua Wang Ke Zen Limin Li
author_facet	Fangfang Jin Yanbo Wang Yanan Zhu Shan Li Ying Liu Cheng Chen Xiaohua Wang Ke Zen Limin Li
author_sort	Fangfang Jin
title	The miR-125a/HK2 axis regulates cancer cell energy metabolism reprogramming in hepatocellular carcinoma
title_short	The miR-125a/HK2 axis regulates cancer cell energy metabolism reprogramming in hepatocellular carcinoma
title_full	The miR-125a/HK2 axis regulates cancer cell energy metabolism reprogramming in hepatocellular carcinoma
title_fullStr	The miR-125a/HK2 axis regulates cancer cell energy metabolism reprogramming in hepatocellular carcinoma
title_full_unstemmed	The miR-125a/HK2 axis regulates cancer cell energy metabolism reprogramming in hepatocellular carcinoma
title_sort	mir-125a/hk2 axis regulates cancer cell energy metabolism reprogramming in hepatocellular carcinoma
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0a1c7709519d43c2ab6c9d02a8031c76
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The miR-125a/HK2 axis regulates cancer cell energy metabolism reprogramming in hepatocellular carcinoma

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