Details

Autor(en) / Beteiligte

• Ling, Hui
• Spizzo, Riccardo
• Atlasi, Yaser
• Nicoloso, Milena
• Shimizu, Masayoshi
• Redis, Roxana S
• Nishida, Naohiro
• Gafà, Roberta
• Song, Jian
• Guo, Zhiyi
• Ivan, Cristina
• Barbarotto, Elisa
• De Vries, Ingrid
• Zhang, Xinna
• Ferracin, Manuela
• Churchman, Mike
• van Galen, Janneke F
• Beverloo, Berna H
• Shariati, Maryam
• Haderk, Franziska
• Estecio, Marcos R
• Garcia-Manero, Guillermo
• Patijn, Gijs A
• Gotley, David C
• Bhardwaj, Vikas
• Shureiqi, Imad
• Sen, Subrata
• Multani, Asha S
• Welsh, James
• Yamamoto, Ken
• Taniguchi, Itsuki
• Song, Min-Ae
• Gallinger, Steven
• Casey, Graham
• Thibodeau, Stephen N
• Le Marchand, Loïc
• Tiirikainen, Maarit
• Mani, Sendurai A
• Zhang, Wei
• Davuluri, Ramana V
• Mimori, Koshi
• Mori, Masaki
• Sieuwerts, Anieta M
• Martens, John W M
• Tomlinson, Ian
• Negrini, Massimo
• Berindan-Neagoe, Ioana
• Foekens, John A
• Hamilton, Stanley R
• Lanza, Giovanni
• Kopetz, Scott
• Fodde, Riccardo
• Calin, George A

Titel

CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer

Ist Teil von

• Genome research, 2013-09, Vol.23 (9), p.1446-1461

Ort / Verlag

United States

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 (lncRNA) encompassing the rs6983267 SNP, is highly overexpressed in microsatellite-stable colorectal cancer and promotes tumor growth, metastasis, and chromosomal instability. We demonstrate that MYC, miR-17-5p, and miR-20a are up-regulated by CCAT2 through TCF7L2-mediated transcriptional regulation. We further identify the physical interaction between CCAT2 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 CCAT2 expression and the risk allele G produces more CCAT2 transcript. Our results support a new mechanism of MYC and WNT regulation by the novel lncRNA CCAT2 in colorectal cancer pathogenesis, and provide an alternative explanation of the SNP-conferred cancer risk.