Knockdown of anion exchanger 2 suppressed the growth of ovarian cancer cells via mTOR/p70S6K1 signaling

Abstract Anion exchanger 2 (AE2, encoded by SLC4A2) is a sodium-independent chloride/bicarbonate transporter and implicated in the regulation of intracellular pH and membrane potential. Previous studies have linked AE2 to the tumorigenesis of various cancers. Here, AE2 was identified as an up-regula...

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Autores principales:	Li-Jun Zhang, Renquan Lu, Ya-Nan Song, Jian-Yong Zhu, Wei Xia, Miao Zhang, Zhi-Yi Shao, Yan Huang, Yuqi Zhou, Hongqin Zhang, Lin Guo, Meiqin Zhang, Hong Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/884a62e5171a4872aaeebe1fa5c0f93e
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spelling	oai:doaj.org-article:884a62e5171a4872aaeebe1fa5c0f93e2021-12-02T12:30:35ZKnockdown of anion exchanger 2 suppressed the growth of ovarian cancer cells via mTOR/p70S6K1 signaling10.1038/s41598-017-06472-w2045-2322https://doaj.org/article/884a62e5171a4872aaeebe1fa5c0f93e2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06472-whttps://doaj.org/toc/2045-2322Abstract Anion exchanger 2 (AE2, encoded by SLC4A2) is a sodium-independent chloride/bicarbonate transporter and implicated in the regulation of intracellular pH and membrane potential. Previous studies have linked AE2 to the tumorigenesis of various cancers. Here, AE2 was identified as an up-regulated protein in ovarian cancer tissues compared to adjacent non-tumor lesions based on quantitative proteomics analysis. AE2 mRNA was also overexpressed in human ovarian cancer samples, and that AE2 overexpression correlated with the shortened survival time of ovarian cancer patients. Short-hairpin RNA-mediated knockdown of AE2 in A2780 and SK-OV-R3 cells inhibited cell growth and induced cell cycle G1 phase arrest. In nude mice, its stable knockdown inhibited the tumorigenicity of A2780 cells. Gene set enrichment analysis on The Cancer Genome Atlas dataset identified that the cell cycle process and mTOR pathway were correlatively with the AE2 expression. Expression of key regulators of G1/S transition (Cyclin D1 and CDK4), and phosphorylation levels of p70S6K were notably reduced in AE2 knockdown cells. Moreover, experiments with mTOR inhibitor suggested that AE2 may promote cell cycle progression through mTOR/p70S6K1 pathway. Together, our results suggest up-regulated AE2 promotes ovarian cancer tumorigenesis by activating mTOR/p70S6K1 pathway and implicate the potential application of AE2 in cancer therapy.Li-Jun ZhangRenquan LuYa-Nan SongJian-Yong ZhuWei XiaMiao ZhangZhi-Yi ShaoYan HuangYuqi ZhouHongqin ZhangLin GuoMeiqin ZhangHong ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Li-Jun Zhang Renquan Lu Ya-Nan Song Jian-Yong Zhu Wei Xia Miao Zhang Zhi-Yi Shao Yan Huang Yuqi Zhou Hongqin Zhang Lin Guo Meiqin Zhang Hong Zhang Knockdown of anion exchanger 2 suppressed the growth of ovarian cancer cells via mTOR/p70S6K1 signaling
description	Abstract Anion exchanger 2 (AE2, encoded by SLC4A2) is a sodium-independent chloride/bicarbonate transporter and implicated in the regulation of intracellular pH and membrane potential. Previous studies have linked AE2 to the tumorigenesis of various cancers. Here, AE2 was identified as an up-regulated protein in ovarian cancer tissues compared to adjacent non-tumor lesions based on quantitative proteomics analysis. AE2 mRNA was also overexpressed in human ovarian cancer samples, and that AE2 overexpression correlated with the shortened survival time of ovarian cancer patients. Short-hairpin RNA-mediated knockdown of AE2 in A2780 and SK-OV-R3 cells inhibited cell growth and induced cell cycle G1 phase arrest. In nude mice, its stable knockdown inhibited the tumorigenicity of A2780 cells. Gene set enrichment analysis on The Cancer Genome Atlas dataset identified that the cell cycle process and mTOR pathway were correlatively with the AE2 expression. Expression of key regulators of G1/S transition (Cyclin D1 and CDK4), and phosphorylation levels of p70S6K were notably reduced in AE2 knockdown cells. Moreover, experiments with mTOR inhibitor suggested that AE2 may promote cell cycle progression through mTOR/p70S6K1 pathway. Together, our results suggest up-regulated AE2 promotes ovarian cancer tumorigenesis by activating mTOR/p70S6K1 pathway and implicate the potential application of AE2 in cancer therapy.
format	article
author	Li-Jun Zhang Renquan Lu Ya-Nan Song Jian-Yong Zhu Wei Xia Miao Zhang Zhi-Yi Shao Yan Huang Yuqi Zhou Hongqin Zhang Lin Guo Meiqin Zhang Hong Zhang
author_facet	Li-Jun Zhang Renquan Lu Ya-Nan Song Jian-Yong Zhu Wei Xia Miao Zhang Zhi-Yi Shao Yan Huang Yuqi Zhou Hongqin Zhang Lin Guo Meiqin Zhang Hong Zhang
author_sort	Li-Jun Zhang
title	Knockdown of anion exchanger 2 suppressed the growth of ovarian cancer cells via mTOR/p70S6K1 signaling
title_short	Knockdown of anion exchanger 2 suppressed the growth of ovarian cancer cells via mTOR/p70S6K1 signaling
title_full	Knockdown of anion exchanger 2 suppressed the growth of ovarian cancer cells via mTOR/p70S6K1 signaling
title_fullStr	Knockdown of anion exchanger 2 suppressed the growth of ovarian cancer cells via mTOR/p70S6K1 signaling
title_full_unstemmed	Knockdown of anion exchanger 2 suppressed the growth of ovarian cancer cells via mTOR/p70S6K1 signaling
title_sort	knockdown of anion exchanger 2 suppressed the growth of ovarian cancer cells via mtor/p70s6k1 signaling
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/884a62e5171a4872aaeebe1fa5c0f93e
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Knockdown of anion exchanger 2 suppressed the growth of ovarian cancer cells via mTOR/p70S6K1 signaling

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