Arid
DOI10.1101/gr.152942.112
CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer
Ling, Hui1; Spizzo, Riccardo1; Atlasi, Yaser2; Nicoloso, Milena1; Shinnizu, Masayoshi1; Redis, Roxana S.1,3; Nishida, Naohiro1,4; Gafa, Roberta5,6; Song, Jian7; Guo, Zhiyi1; Ivan, Cristina8; Barbarotto, Elisa1; De Vries, Ingrid2; Zhang, Xinna8; Ferracin, Manuela5,6; Churchman, Mike9; van Galen, Janneke F.10; Beverloo, Berna H.10; Shariati, Maryam11; Haderk, Franziska1; Estecio, Marcos R.12,13; Garcia-Manero, Guillermo14; Patijn, Gijs A.2; Gotley, David C.15; Bhardwaj, Vikas16; Shureiqi, Imad7; Sen, Subrata11; Multani, Asha S.17; Welsh, James16; Yamamoto, Ken18; Taniguchi, Itsuki18; Song, Min-Ae19; Gallinger, Steven20; Casey, Graham21; Thibodeau, Stephen N.22; Le Marchand, Loic23; Tiirikainen, Maarit24; Mani, Sendurai A.11; Zhang, Wei25; Davuluri, Ramana V.26; Mimori, Koshi27; Mori, Masaki4; Sieuwerts, Anieta M.28; Martens, John W. M.28; Tomlinson, Ian9; Negrini, Massimo5,6; Berindan-Neagoe, Ioana29,30; Foekens, John A.28; Hamilton, Stanley R.25; Lanza, Giovanni5,6; Kopetz, Scott7; Fodde, Riccardo2; Calin, George A.1,8
通讯作者Calin, George A.
来源期刊GENOME RESEARCH
ISSN1088-9051
EISSN1549-5469
出版年2013
卷号23期号:9页码:1446-1461
英文摘要

The functional roles of SNPs within the 8q24 gene desert in the cancer phenotype are not yet well understood. Here, we report that CCAT2, a novel long noncoding RNA transcript (IncRNA) encompassing the rs6983267 SNP, is highly over-expressed in microsatellite-stable colorectal cancer and promotes tumor growth, metastasis, and chromosomal instability. We demonstrate that MY, miR-17-5p, and miR-20a are up-regulated by CCAT2 through TCF7L2-mediated transcriptional regulation. We further identify the physical interaction between CC4T2 and TCF7L2 resulting in an enhancement of WNT signaling activity. We show that CCAT2 is itself a WNT downstream target, which suggests the existence of a feedback loop. Finally, we demonstrate that the SNP status affects CC4T2 expression and the risk allele G produces more CCAT2 transcript. Our results support a new mechanism of MYC and WNT regulation by the novel IncRNA CCAT2 in colorectal cancer pathogenesis, and provide an alternative explanation of the SNP-conferred cancer risk.


类型Article
语种英语
国家USA ; Netherlands ; Romania ; Japan ; Italy ; England ; Australia ; Canada
收录类别SCI-E
WOS记录号WOS:000324080000008
WOS关键词C-MYC ; COLORECTAL-CANCER ; SNP RS6983267 ; BETA-CATENIN ; APC ; TRANSCRIPTION ; EXPRESSION ; MICRORNAS ; PROTEIN ; TARGET
WOS类目Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Genetics & Heredity
WOS研究方向Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Genetics & Heredity
来源机构University of Oxford
资源类型期刊论文
条目标识符http://119.78.100.177/qdio/handle/2XILL650/177289
作者单位1.Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA;
2.Erasmus MC, Josephine Nefkens Inst, Dept Pathol, NL-3000 CA Rotterdam, Netherlands;
3.Univ Med & Pharm I Hatieganu, Dept Med Genet, Cluj Napoca 400023, Romania;
4.Osaka Univ, Grad Sch Med, Dept Surg Gastroenterol, Suita, Osaka 5650871, Japan;
5.Univ Ferrara, Dept Expt & Diagnost Med, I-44121 Ferrara, Italy;
6.Univ Ferrara, LTTA, I-44121 Ferrara, Italy;
7.Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA;
8.Univ Texas MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNAs, Houston, TX 77030 USA;
9.Univ Oxford, NIHR Comprehens Biomed Res Ctr, Welcome Trust Ctr Human Genet, Oxford OX1 2JD, England;
10.Erasmus MC, Dept Clin Genet, Josephine Nefkens Inst, NL-3000 CA Rotterdam, Netherlands;
11.Univ Texas MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA;
12.Univ Texas MD Anderson Canc Ctr, Dept Mol Carcinogenesis, Houston, TX 77030 USA;
13.Univ Texas MD Anderson Canc Ctr, Ctr Canc Epigenet, Houston, TX 77030 USA;
14.Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA;
15.Princess Alexandra Hosp, Dept Surg, Brisbane, Qld 4102, Australia;
16.Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA;
17.Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA;
18.Kyushu Univ, Div Genome Anal, Res Ctr Genet Informat, Med Inst Bioregulat, Fukuoka 8128582, Japan;
19.Univ Hawaii Manoa, Dept Mol Biosci & Bioengn, Honolulu, HI 96822 USA;
20.Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Surg, Toronto, ON MSG 1X5, Canada;
21.Univ So Calif, Keck Sch Med, Dept Prevent Med, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90089 USA;
22.Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA;
23.Univ Hawaii, Program Epidemiol, Ctr Canc, Honolulu, HI 96813 USA;
24.Univ Hawaii, Ctr Canc, Honolulu, HI 96813 USA;
25.Univ Texas MD Anderson Canc Ctr, Dept Pathol, Div Pathol & Lab Med, Houston, TX 77030 USA;
26.Wistar Inst Anat & Biol, Ctr Syst & Computat Biol, Philadelphia, PA 19104 USA;
27.Kyushu Univ, Beppu Hosp, Dept Surg, Beppu, Oita 8740838, Japan;
28.Erasmus Univ, Dept Med Oncol, Med Ctr, Dr Daniel Den Hoed Canc Ctr, NL-3000 CA Rotterdam, Netherlands;
29.Univ Med & Pharm I Hatieganu, Dept Immunol, Cluj Napoca 400023, Romania;
30.Univ Med & Pharm I Hatieganu, Res Ctr Funct Genom Biomed & Translat Med, Cluj Napoca 400023, Romania
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Ling, Hui,Spizzo, Riccardo,Atlasi, Yaser,et al. CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer[J]. University of Oxford,2013,23(9):1446-1461.
APA Ling, Hui.,Spizzo, Riccardo.,Atlasi, Yaser.,Nicoloso, Milena.,Shinnizu, Masayoshi.,...&Calin, George A..(2013).CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer.GENOME RESEARCH,23(9),1446-1461.
MLA Ling, Hui,et al."CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer".GENOME RESEARCH 23.9(2013):1446-1461.
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