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学科主题: 临床医学
题名:
CFTR suppresses tumor progression through miR-193b targeting urokinase plasminogen activator (uPA) in prostate cancer
作者: Xie, C.1; Jiang, X. H.1,2; Zhang, J. T.1; Sun, T. T.1; Dong, J. D.1; Sanders, A. J.3; Diao, R. Y.1,4; Wang, Y.1; Fok, K. L.1; Tsang, L. L.1; Yu, M. K.1; Zhang, X. H.1; Chung, Y. W.1; Ye, L.3; Zhao, M. Y.1; Guo, J. H.1; Xiao, Z. J.1; Lan, H. Y.5; Ng, C. F.6; Lau, K. M.7; Cai, Z. M.4; Jiang, W. G.3; Chan, H. C.1,2,8
关键词: CFTR ; miR-193b ; uPA
刊名: ONCOGENE
发表日期: 2013-05-01
DOI: 10.1038/onc.2012.251
卷: 32, 期:18, 页:2282-2291
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
研究领域[WOS]: Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
关键词[WOS]: TRANSMEMBRANE CONDUCTANCE REGULATOR ; CYSTIC-FIBROSIS GENE ; NF-KAPPA-B ; BREAST-CANCER ; PANCREATIC ADENOCARCINOMA ; HEPATOCELLULAR-CARCINOMA ; MESENCHYMAL TRANSITION ; MUC4 EXPRESSION ; CELL MIGRATION ; MIR-200 FAMILY
英文摘要:

Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is expressed in the epithelial cells of a wide range of organs/tissues from which most cancers are derived. Although accumulating reports have indicated the association of cancer incidence with genetic variations in CFTR gene, the exact role of CFTR in cancer development and the possible underlying mechanism have not been elucidated. Here, we report that CFTR expression is significantly decreased in both prostate cancer cell lines and human prostate cancer tissue samples. Overexpression of CFTR in prostate cancer cell lines suppresses tumor progression (cell growth, adhesion and migration), whereas knockdown of CFTR leads to enhanced malignancies both in vitro and in vivo. In addition, we demonstrate that CFTR knockdown-enhanced cell proliferation, cell invasion and migration are significantly reversed by antibodies against either urokinase plasminogen activator (uPA) or uPA receptor (uPAR), which are known to be involved in various malignant traits of cancer development. More interestingly, overexpression of CFTR suppresses uPA by upregulating the recently described tumor suppressor microRNA-193b (miR-193b), and overexpression of pre-miR-193b significantly reverses CFTR knockdown-enhanced malignant phenotype and abrogates elevated uPA activity in prostate cancer cell line. Finally, we show that CFTR gene transfer results in significant tumor repression in prostate cancer xenografts in vivo. Taken together, the present study has demonstrated a previously undefined tumor-suppressing role of CFTR and its involvement in regulation of miR-193b in prostate cancer development.

语种: 英语
所属项目编号: 2012CB944900 ; GRF-CUHK466111
项目资助者: Focused Investment Scheme of the Chinese University of Hong Kong and National 973 project ; Fundamental Research Funds for the Central Universities (JiNan University)
WOS记录号: WOS:000318683600005
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53546
Appears in Collections:北京大学深圳医院_期刊论文

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作者单位: 1.Chinese Univ Hong Kong, Sch Biomed Sci, Epithelial Cell Biol Res Ctr, Shatin, Hong Kong, Peoples R China
2.Chinese Univ Hong Kong, Minist Educ Peoples Republ China, Key Lab Regenerat Med, Jinan Univ, Guangzhou, Guangdong, Peoples R China
3.Cardiff Univ, Sch Med, Metastasis & Angiogenesis Res Grp, Dept Surg, Cardiff CF10 3AX, S Glam, Wales
4.Peking Univ, Shenzhen Hosp, Shenzhen Key Lab Male Reprod Med & Genet, Shenzhen, Peoples R China
5.Chinese Univ Hong Kong, Fac Med, Dept Med & Therapeut, Li Ka Shing Inst Hlth Sci, Shatin, Hong Kong, Peoples R China
6.Chinese Univ Hong Kong, Div Urol, Dept Surg, Shatin, Hong Kong, Peoples R China
7.Chinese Univ Hong Kong, Prince Wales Hosp, Dept Anat & Cellular Pathol, Shatin, Hong Kong, Peoples R China
8.Sichuan Univ, Chinese Univ Hong Kong, West China Second Univ Hosp, Joint Lab Reprod Med, Chengdu 610064, Peoples R China

Recommended Citation:
Xie, C.,Jiang, X. H.,Zhang, J. T.,et al. CFTR suppresses tumor progression through miR-193b targeting urokinase plasminogen activator (uPA) in prostate cancer[J]. ONCOGENE,2013,32(18):2282-2291.
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