p85 alpha promotes nucleolin transcription and subsequently enhances EGFR mRNA stability and EGF-induced malignant cellular transformation

doi:10.18632/oncotarget.7674

科研成果详情

题名	p85 alpha promotes nucleolin transcription and subsequently enhances EGFR mRNA stability and EGF-induced malignant cellular transformation
作者	Xie, Qipeng1; Guo, Xirui 1; Gu, Jiayan 1; Zhang, Liping 1; Jin, Honglei 1,2; Huang, Haishan1; Li, Jingxia 2; Huang, Chuanshu1,2
发表日期	2016-03-29
发表期刊	ONCOTARGET 影响因子和分区
语种	英语
原始文献类型	Article
关键词	PI3K p85 alpha EGFR nucleolin cell transformation
其他关键词	EPIDERMAL-GROWTH-FACTOR ; P85 REGULATORY SUBUNIT ; AU-RICH ELEMENTS ; POSTTRANSCRIPTIONAL REGULATION ; 3'-UNTRANSLATED REGION ; CONDITIONAL KNOCKOUT ; PROTEIN-DEGRADATION ; APOPTOTIC RESPONSE ; COLORECTAL-CANCER ; TYROSINE KINASES
摘要	p85 alpha is a regulatory subunit of phosphatidylinositol 3-kinase (PI3K) that is a key lipid enzyme for generating phosphatidylinositol 3, 4, 5-trisphosphate, and subsequently activates signaling that ultimately regulates cell cycle progression, cell growth, cytoskeletal changes, and cell migration. In addition to form a complex with the p110 catalytic subunit, p85 alpha also exists as a monomeric form due to that there is a greater abundance of p85 alpha than p110 in many cell types. Our previous studies have demonstrated that monomeric p85 alpha exerts a pro-apoptotic role in UV response through induction of TNF-alpha gene expression in PI3K-independent manner. In current studies, we identified a novel biological function of p85 alpha as a positive regulator of epidermal growth factor receptor (EGFR) expression and cell malignant transformation via nucleolin-dependent mechanism. Our results showed that p85 alpha was crucial for EGFR and nucleolin expression and subsequently resulted in an increase of malignant cellular transformation by using both specific knockdown and deletion of p85 alpha in its normal expressed cells. Mechanistic studies revealed that p85 alpha upregulated EGFR protein expression mainly through stabilizing its mRNA, whereas nucleolin (NCL) was able to bind to egfr mRNA and increase its mRNA stability. Consistently, overexpression of NCL in p85 alpha-/- cells restored EGFR mRNA stabilization, protein expression and cell malignant transformation. Moreover, we discovered that p85 alpha upregulated NCL gene transcription via enhancing C-Jun activation. Collectively, our studies demonstrate a novel function of p85 alpha as a positive regulator of EGFR mRNA stability and cell malignant transformation, providing a significant insight into the understanding of biomedical nature of p85 alpha protein in mammalian cells and further supporting that p85 alpha might be a potential target for cancer prevention and therapy.
资助项目	NIH/NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [CA112557, CA165980, CA177665]; NIH/NIEHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Environmental Health Sciences (NIEHS) [ES000260]; Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [NSFC81229002, NSFC81372946]; Key Project of Science and Technology Innovation Team of Zhejiang Province [2013TD10]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P01CA165980, R01CA177665, R01CA112557] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Environmental Health Sciences (NIEHS) [P30ES000260] Funding Source: NIH RePORTER
出版者	IMPACT JOURNALS LLC
出版地	ORCHARD PARK
ISSN	1949-2553
EISSN	1949-2553
卷号	7 期号:13 页码:16636-16649
DOI	10.18632/oncotarget.7674
页数	14
WOS类目	Oncology ; Cell Biology
WOS研究方向	Oncology ; Cell Biology
WOS记录号	WOS:000375692900102
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	26918608
PMC记录号	PMC4941340
SCOPUSEID	2-s2.0-84971597350
通讯作者地址	[Huang, Chuanshu]Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms,School of Life Sciences,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China
Scopus学科分类	Oncology
引用统计	被引频次：20[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/16692
专题	检验医学院（生命科学学院、生物学实验教学中心）_模式生物技术与应用重点实验室
通讯作者	Huang, Chuanshu
作者单位	1.Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms,School of Life Sciences,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China; 2.Nelson Institute of Environmental Medicine,New York University School of Medicine,Tuxedo,10987,United States
第一作者单位	模式生物技术与应用重点实验室; 检验医学院（生命科学学院、生物学实验教学中心）
通讯作者单位	模式生物技术与应用重点实验室; 检验医学院（生命科学学院、生物学实验教学中心）
第一作者的第一单位	模式生物技术与应用重点实验室
推荐引用方式 GB/T 7714	Xie, Qipeng,Guo, Xirui,Gu, Jiayan,et al. p85 alpha promotes nucleolin transcription and subsequently enhances EGFR mRNA stability and EGF-induced malignant cellular transformation[J]. ONCOTARGET,2016,7(13):16636-16649.
APA	Xie, Qipeng., Guo, Xirui., Gu, Jiayan., Zhang, Liping., Jin, Honglei., ... & Huang, Chuanshu. (2016). p85 alpha promotes nucleolin transcription and subsequently enhances EGFR mRNA stability and EGF-induced malignant cellular transformation. ONCOTARGET, 7(13), 16636-16649.
MLA	Xie, Qipeng,et al."p85 alpha promotes nucleolin transcription and subsequently enhances EGFR mRNA stability and EGF-induced malignant cellular transformation".ONCOTARGET 7.13(2016):16636-16649.