Expression and Transcriptional Regulation of Human ATP6V1A Gene in Gastric Cancers

Abstract Recent studies demonstrate that the invasion and metastasis of gastric cancer (GC) is closely associated with a multi-subunit vacuolar H+-ATPase (V-ATPase). Here we investigated the expression and role of the human ATP6V1A gene that encodes the catalytic subunit A of V-ATPase in GC. We foun...

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Autores principales:	Pin Wang, Lei Wang, Jie Sha, Guochun Lou, Nannan Lu, Bo Hang, Jian-Hua Mao, Xiaoping Zou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dfcb6f3d81fd4a86823aec1a9832449e
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spelling	oai:doaj.org-article:dfcb6f3d81fd4a86823aec1a9832449e2021-12-02T12:32:45ZExpression and Transcriptional Regulation of Human ATP6V1A Gene in Gastric Cancers10.1038/s41598-017-03021-32045-2322https://doaj.org/article/dfcb6f3d81fd4a86823aec1a9832449e2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03021-3https://doaj.org/toc/2045-2322Abstract Recent studies demonstrate that the invasion and metastasis of gastric cancer (GC) is closely associated with a multi-subunit vacuolar H+-ATPase (V-ATPase). Here we investigated the expression and role of the human ATP6V1A gene that encodes the catalytic subunit A of V-ATPase in GC. We found that ATP6V1A expression level is significantly elevated in GCs compared to normals, but GC patients with higher expression levels of ATP6V1A have a better prognosis. Genomic analysis revealed that APT6V1A copy number is gained in a small fraction of GC patients and lost in a minimum number. Moreover, the ATP6V1A copy number was positively correlated with its mRNA level. To explore additional mechanisms by which ATP6V1A overexpressed in GCs, we investigated the relationship between transcription factor YY1 and ATP6V1A, and found that mRNA expression of YY1 had significant correlation with that of ATP6V1A. To validate that YY1 transcriptionally regulates ATP6V1A, we discovered that the ATP6V1A core promoter region contains three YY1 binding sites. Moreover, RNAi-mediated knockdown of YY1 in GC cells significantly decreased ATP6V1A mRNA and protein expression, while YY1 overexpression increased ATP6V1A expression level. In conclusion, YY1 may play an important regulatory role in ATP6V1A expression with potential mechanistic and clinical implications in GC.Pin WangLei WangJie ShaGuochun LouNannan LuBo HangJian-Hua MaoXiaoping ZouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pin Wang Lei Wang Jie Sha Guochun Lou Nannan Lu Bo Hang Jian-Hua Mao Xiaoping Zou Expression and Transcriptional Regulation of Human ATP6V1A Gene in Gastric Cancers
description	Abstract Recent studies demonstrate that the invasion and metastasis of gastric cancer (GC) is closely associated with a multi-subunit vacuolar H+-ATPase (V-ATPase). Here we investigated the expression and role of the human ATP6V1A gene that encodes the catalytic subunit A of V-ATPase in GC. We found that ATP6V1A expression level is significantly elevated in GCs compared to normals, but GC patients with higher expression levels of ATP6V1A have a better prognosis. Genomic analysis revealed that APT6V1A copy number is gained in a small fraction of GC patients and lost in a minimum number. Moreover, the ATP6V1A copy number was positively correlated with its mRNA level. To explore additional mechanisms by which ATP6V1A overexpressed in GCs, we investigated the relationship between transcription factor YY1 and ATP6V1A, and found that mRNA expression of YY1 had significant correlation with that of ATP6V1A. To validate that YY1 transcriptionally regulates ATP6V1A, we discovered that the ATP6V1A core promoter region contains three YY1 binding sites. Moreover, RNAi-mediated knockdown of YY1 in GC cells significantly decreased ATP6V1A mRNA and protein expression, while YY1 overexpression increased ATP6V1A expression level. In conclusion, YY1 may play an important regulatory role in ATP6V1A expression with potential mechanistic and clinical implications in GC.
format	article
author	Pin Wang Lei Wang Jie Sha Guochun Lou Nannan Lu Bo Hang Jian-Hua Mao Xiaoping Zou
author_facet	Pin Wang Lei Wang Jie Sha Guochun Lou Nannan Lu Bo Hang Jian-Hua Mao Xiaoping Zou
author_sort	Pin Wang
title	Expression and Transcriptional Regulation of Human ATP6V1A Gene in Gastric Cancers
title_short	Expression and Transcriptional Regulation of Human ATP6V1A Gene in Gastric Cancers
title_full	Expression and Transcriptional Regulation of Human ATP6V1A Gene in Gastric Cancers
title_fullStr	Expression and Transcriptional Regulation of Human ATP6V1A Gene in Gastric Cancers
title_full_unstemmed	Expression and Transcriptional Regulation of Human ATP6V1A Gene in Gastric Cancers
title_sort	expression and transcriptional regulation of human atp6v1a gene in gastric cancers
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/dfcb6f3d81fd4a86823aec1a9832449e
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_version_	1718394011323990016

Expression and Transcriptional Regulation of Human ATP6V1A Gene in Gastric Cancers

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