LncRNA GClnc1 Promotes Gastric Carcinogenesis and May Act as a Modular Scaffold of WDR5 and KAT2A Complexes to Specify the Histone Modification Pattern

被引：341

作者：

Sun, Tian-Tian ^{[1
]}

He, Jie ^{[2
,3
]}

Liang, Qian ^{[1
]}

Ren, Lin-Lin ^{[1
]}

Yan, Ting-Ting ^{[1
]}

Yu, Ta-Chung ^{[1
]}

Tang, Jia-Yin ^{[1
]}

Bao, Yu-Jie ^{[1
]}

Hu, Ye ^{[1
]}

Lin, Yanwei ^{[1
,4
]}

Sun, Danfeng ^{[1
,4
]}

Chen, Ying-Xuan ^{[1
]}

Hong, Jie ^{[1
]}

Chen, Haoyan ^{[1
]}

Zou, Weiping ^{[4
]}

Fang, Jing-Yuan ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med,Shanghai Canc Inst,Shanghai Inst Digest D, Minist Hlth,Div Gastroenterol & Hepatol,Ren Ji Ho, State Key Lab Oncogenes & Related Genes,Key Lab G, Shanghai, Peoples R China

[2] Guangzhou Med Univ, Dept Gastroenterol, Guangzhou, Guangdong, Peoples R China

[3] Guangzhou Med Univ, Guangzhou Peoples Hosp 1, Guangzhou Digest Dis Ctr, Guangzhou Key Lab Digest Dis, Guangzhou, Guangdong, Peoples R China

[4] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI 48109 USA

来源：

CANCER DISCOVERY | 2016年 / 6卷 / 07期

基金：

中国国家自然科学基金;

关键词：

LONG NONCODING RNA; POOR-PROGNOSIS; CANCER; GENE; SOD2; PROLIFERATION; TRANSCRIPTION; EXPRESSION; PROTEINS; DOMAINS;

D O I：

10.1158/2159-8290.CD-15-0921

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Long noncoding RNAs (lncRNA) play a role in carcinogenesis. However, the function of lncRNAs in human gastric cancer remains largely unknown. In this study, we identified a novel lncRNA, GClnc1, which was upregulated and associated with tumorigenesis, tumor size, metastasis, and poor prognosis in gastric cancer. GClnc1 affected gastric cancer cell proliferation, invasiveness, and metastasis in multiple gastric cancer models. Mechanistically, GClnc1 bound WDR5 (a key component of histone methyltransferase complex) and KAT2A histone acetyltransferase, acted as a modular scaffold of WDR5 and KAT2A complexes, coordinated their localization, specified the histone modification pattern on the target genes, including SOD2, and consequently altered gastric cancer cell biology. Thus, GClnc1 is mechanistically, functionally, and clinically oncogenic in gastric cancer. Targeting GClnc1 and its pathway may be meaningful for treating patients with gastric cancer. SIGNIFICANCE: This report documents a novel lncRNA, GClnc1, which may act as a scaffold to recruit the WDR5 and KAT2A complex and modify the transcription of target genes. This study reveals that GClnc1 is an oncogenic lncRNA in human gastric cancer. (C) 2016 AACR.

引用

页码：784 / 801

页数：18

共 50 条

[1] Comprehensive molecular characterization of gastric adenocarcinoma [J].

Bass, Adam J. ;

Thorsson, Vesteinn ;

Shmulevich, Ilya ;

Reynolds, Sheila M. ;

Miller, Michael ;

Bernard, Brady ;

Hinoue, Toshinori ;

Laird, Peter W. ;

Curtis, Christina ;

Shen, Hui ;

Weisenberger, Daniel J. ;

Schultz, Nikolaus ;

Shen, Ronglai ;

Weinhold, Nils ;

Keiser, David P. ;

Bowlby, Reanne ;

Sipahimalani, Payal ;

Cherniack, Andrew D. ;

Getz, Gad ;

Liu, Yingchun ;

Noble, Michael S. ;

Pedamallu, Chandra ;

Sougnez, Carrie ;

Taylor-Weiner, Amaro ;

Akbani, Rehan ;

Lee, Ju-Seog ;

Liu, Wenbin ;

Mills, Gordon B. ;

Yang, Da ;

Zhang, Wei ;

Pantazi, Angeliki ;

Parfenov, Michael ;

Gulley, Margaret ;

Piazuelo, M. Blanca ;

Schneider, Barbara G. ;

Kim, Jihun ;

Boussioutas, Alex ;

Sheth, Margi ;

Demchok, John A. ;

Rabkin, Charles S. ;

Willis, Joseph E. ;

Ng, Sam ;

Garman, Katherine ;

Beer, David G. ;

Pennathur, Arjun ;

Raphael, Benjamin J. ;

Wu, Hsin-Ta ;

Odze, Robert ;

Kim, Hark K. ;

Bowen, Jay .

NATURE, 2014, 513 (7517) :202-209

[2] Epigenetic programming of the rRNA promoter by MBD3 [J].

Brown, Shelley E. ;

Szyf, Moshe .

MOLECULAR AND CELLULAR BIOLOGY, 2007, 27 (13) :4938-4952

[3] Activation of NF-B by SOD2 promotes the aggressiveness of lung adenocarcinoma by modulating NKX2-1-mediated IKK expression [J].

Chen, Po-Ming ;

Wu, Tzu-Chin ;

Wang, Yao-Chen ;

Cheng, Ya-Wen ;

Sheu, Gwo-Tarng ;

Chen, Chih-Yi ;

Lee, Huei .

CARCINOGENESIS, 2013, 34 (11) :2655-2663

[4] Chromatin Isolation by RNA Purification (ChIRP) [J].

Chu, Ci ;

Quinn, Jeffrey ;

Chang, Howard Y. .

JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2012, (61)

[5] Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer [J].

Cunningham, David ;

Allum, William H. ;

Stenning, Sally P. ;

Thompson, Jeremy N. ;

Van de Velde, Cornelis J. H. ;

Nicolson, Marianne ;

Scarffe, J. Howard ;

Lofts, Fiona J. ;

Falk, Stephen J. ;

Iveson, Timothy J. ;

Smith, David B. ;

Langley, Ruth E. ;

Verma, Monica ;

Weeden, Simon ;

Chua, Yu Jo .

NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (01) :11-20

[6] A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets [J].

Deng, Niantao ;

Goh, Liang Kee ;

Wang, Hannah ;

Das, Kakoli ;

Tao, Jiong ;

Tan, Iain Beehuat ;

Zhang, Shenli ;

Lee, Minghui ;

Wu, Jeanie ;

Lim, Kiat Hon ;

Lei, Zhengdeng ;

Goh, Glenn ;

Lim, Qing-Yan ;

Tan, Angie Lay-Keng ;

Poh, Dianne Yu Sin ;

Riahi, Sudep ;

Bell, Sandra ;

Shi, Michael M. ;

Linnartz, Ronald ;

Zhu, Feng ;

Yeoh, Khay Guan ;

Toh, Han Chong ;

Yong, Wei Peng ;

Cheong, Hyun Cheol ;

Rha, Sun Young ;

Boussioutas, Alex ;

Grabsch, Heike ;

Rozen, Steve ;

Tan, Patrick .

GUT, 2012, 61 (05) :673-684

[7] Enhanced Expression of Long Non-Coding RNA HOTAIR Is Associated with the Development of Gastric Cancer [J].

Endo, Hiroyuki ;

Shiroki, Takeharu ;

Nakagawa, Takayuki ;

Yokoyama, Misa ;

Tamai, Keiichi ;

Yamanami, Hideaki ;

Fujiya, Tsuneaki ;

Sato, Ikuro ;

Yamaguchi, Kazunori ;

Tanaka, Nobuyuki ;

Iijima, Katsunori ;

Shimosegawa, Tooru ;

Sugamura, Kazuo ;

Satoh, Kennichi .

PLOS ONE, 2013, 8 (10)

[8] The gene regulatory networks controlled by estrogens [J].

Gao, Hui ;

Dahlman-Wright, Karin .

MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2011, 334 (1-2) :83-90

[9] lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elements [J].

Gong, Chenguang ;

Maquat, Lynne E. .

NATURE, 2011, 470 (7333) :284-+

[10] 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

← 1 2 3 4 5 →