linc-UBC1 physically associates with polycomb repressive complex 2 (PRC2) and acts as a negative prognostic factor for lymph node metastasis and survival in bladder cancer

被引：133

作者：

He, Wang ^{[1
]}

Cai, Qingqing ^{[2
]}

Sun, Fenyong ^{[3
]}

Zhong, Guangzheng ^{[1
]}

Wang, Pei ^{[1
]}

Liu, Hongyan ^{[4
]}

Luo, Junhua ^{[1
]}

Yu, Hao ^{[1
]}

Huang, Jian ^{[1
]}

Lin, Tianxin ^{[1
,5
]}

机构：

[1] Sun Yat Sen Mem Hosp, Dept Urol, Guangzhou, Guangdong, Peoples R China

[2] Sun Yat Sen Univ, Ctr Canc, Dept Internal Med, Guangzhou 510275, Guangdong, Peoples R China

[3] Tongji Univ, Dept Lab, Shanghai Peoples Hosp 10, Hospitatal 10, Shanghai 200092, Peoples R China

[4] Gaozhou Hosp, Dept Med Ultrason, Maoming, Peoples R China

[5] Sun Yat Sen Univ, Lin Bai Xin Res Ctr, Sun Yat Sen Mem Hosp, Guangzhou 510275, Guangdong, Peoples R China

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2013年 / 1832卷 / 10期

基金：

中国国家自然科学基金;

关键词：

Long intergenic noncoding RNA; linc-UBC1; Prognostic factor; Bladder cancer; Polycomb repressive complex 2; NONCODING RNA HOTAIR; GENE-EXPRESSION; SIGNATURE; EZH2; PROGRESSION; GENOME; TUMORS;

D O I：

10.1016/j.bbadis.2013.05.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Objectives: The human genome encodes many long intergenic noncoding RNAs (lincRNAs). However, their biological functions, molecular mechanisms and prognostic values associated with bladder cancer remain to be elucidated. Here we investigated a lincRNA termed linc-UBC1 (Up-regulated in bladder cancer 1) and evaluated its prognostic value in bladder cancer patients. Materials and methods: Expression of linc-UBC1 was evaluated by quantitative reverse transcription PCR (qRT-PCR) in 102 bladder cancer tissue samples and normal adjacent tissues. The functions of linc-UBC1 on cell proliferation, migration, invasion, colony formation, tumorigenicity and metastatic potential were evaluated by knockdown strategy in vitro and in vivo. RNA immunoprecipitation (RIP) was performed to confirm that linc-UBC1 physically associates with EZH2 and SUZ12, core components of polycomb repressive complex 2 (PRO). Chromatin immunoprecipitation (ChIP) was conducted to examine histone modification status. Results: qRT-PCR confirmed that linc-UBC1 expression is up-regulated in 60 cases (58.8%) in bladder cancer tissues compared with normal adjacent tissues, and its overexpression correlates with lymph node metastasis and poor survival. Further functional analysis demonstrated that knockdown of linc-UBC1 attenuates bladder cancer cell proliferation, motility, invasion, colony formation ability, tumorigenicity and metastatic potential. Importantly, the inhibitory effect of linc-UBC1 on cell proliferation was also observed in primary bladder cancer cells obtained from patients. RIP and ChIP assay confirmed that linc-UBC1 physically associates with PRO complex and regulates histone modification status of target genes. Conclusions: Frequently overexpressed linc-UBC1 physically associates with PRC2 complex, and acts as a negative prognostic factor for lymph node metastasis and survival in bladder cancer. (C) 2013 Elsevier B.V. All rights reserved.

引用

页码：1528 / 1537

页数：10

共 25 条

[1] An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors [J].

Ben-Porath, Ittai ;

Thomson, Matthew W. ;

Carey, Vincent J. ;

Ge, Ruping ;

Bell, George W. ;

Regev, Aviv ;

Weinberg, Robert A. .

NATURE GENETICS, 2008, 40 (05) :499-507

[2] Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions [J].

Bracken, AP ;

Dietrich, N ;

Pasini, D ;

Hansen, KH ;

Helin, K .

GENES & DEVELOPMENT, 2006, 20 (09) :1123-1136

[3] Germline prognostic markers for urinary bladder cancer: Obstacles and opportunities [J].

Chang, David W. ;

Gu, Jian ;

Wu, Xifeng .

UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS, 2012, 30 (04) :524-532

[4] Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 [J].

Ferlay, Jacques ;

Shin, Hai-Rim ;

Bray, Freddie ;

Forman, David ;

Mathers, Colin ;

Parkin, Donald Maxwell .

INTERNATIONAL JOURNAL OF CANCER, 2010, 127 (12) :2893-2917

[5]

Frickett J.W., 1982, NUCLEIC ACIDS RES, V10, P5303

[6] Large Intervening Non-coding RNA HOTAIR is Associated with Hepatocellular Carcinoma Progression [J].

Geng, Y. J. ;

Xie, S. L. ;

Li, Q. ;

Ma, J. ;

Wang, G. Y. .

JOURNAL OF INTERNATIONAL MEDICAL RESEARCH, 2011, 39 (06) :2119-2128

[7] Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis [J].

Gupta, Rajnish A. ;

Shah, Nilay ;

Wang, Kevin C. ;

Kim, Jeewon ;

Horlings, Hugo M. ;

Wong, David J. ;

Tsai, Miao-Chih ;

Hung, Tiffany ;

Argani, Pedram ;

Rinn, John L. ;

Wang, Yulei ;

Brzoska, Pius ;

Kong, Benjamin ;

Li, Rui ;

West, Robert B. ;

van de Vijver, Marc J. ;

Sukumar, Saraswati ;

Chang, Howard Y. .

NATURE, 2010, 464 (7291) :1071-U148

[8] Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals [J].

Guttman, Mitchell ;

Amit, Ido ;

Garber, Manuel ;

French, Courtney ;

Lin, Michael F. ;

Feldser, David ;

Huarte, Maite ;

Zuk, Or ;

Carey, Bryce W. ;

Cassady, John P. ;

Cabili, Moran N. ;

Jaenisch, Rudolf ;

Mikkelsen, Tarjei S. ;

Jacks, Tyler ;

Hacohen, Nir ;

Bernstein, Bradley E. ;

Kellis, Manolis ;

Regev, Aviv ;

Rinn, John L. ;

Lander, Eric S. .

NATURE, 2009, 458 (7235) :223-227

[9] Global H3K27 trimethylation and EZH2 abundance in breast tumor subtypes [J].

Holm, Karolina ;

Grabau, Dorthe ;

Lovgren, Kristina ;

Aradottir, Steina ;

Gruvberger-Saal, Sofia ;

Howlin, Jillian ;

Saal, Lao H. ;

Ethier, Stephen P. ;

Bendahl, Par-Ola ;

Stal, Olle ;

Malmstrom, Per ;

Ferno, Marten ;

Ryden, Lisa ;

Hegardt, Cecilia ;

Borg, Ake ;

Ringner, Markus .

MOLECULAR ONCOLOGY, 2012, 6 (05) :494-506

[10] The Impact of Lymphadenectomy and Lymph Node Metastasis on the Outcomes of Radical Cystectomy for Bladder Cancer [J].

Karl, Alexander ;

Carroll, Peter R. ;

Gschwend, Juergen E. ;

Knuechel, Ruth ;

Montorsi, Francesco ;

Stief, Christian G. ;

Studer, Urs E. .

EUROPEAN UROLOGY, 2009, 55 (04) :826-835

← 1 2 3 →