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

Ling, H., Spizzo, R., Atlasi, Y., Nicoloso, M., Shimizu, M., Redis, R. S., Nishida, N., Gafa, R., Song, J., Guo, Z., Ivan, C., Barbarotto, E., De, Vries I., Zhang, X., Ferracin, M., Churchman, M., Van Galen, J. F., Beverloo, B. H., Shariati, M., Haderk, F., Estecio, M. R., Garcia-Manero, G., Patijn, G.A., Gotley, D.C., Bhardwaj, V., Shureiqi, I., Sen, S., Multani, A. S., Welsh, J., Yamamoto, K., Taniguchi, I., Song, M.-A., Gallinger, S., Casey, G., Thibodeau, S.N., Le Marchand, L., Tiirikainen, M., Mani, S.A., Zhang, W., Davuluri, R.V., Mimori, K., Mori, M., Sieuwerts, A.M., Martens, J.W.M., Tomlinson, I., Negrini, M., Berindan-Neagoe, I., Foekens, J.A., Hamilton, S.R., Lanza, G., Kopetz, S., Fodde, R. and Calin, G.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. doi:10.1101/gr.152942.112

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Author Ling, H.
Spizzo, R.
Atlasi, Y.
Nicoloso, M.
Shimizu, M.
Redis, R. S.
Nishida, N.
Gafa, R.
Song, J.
Guo, Z.
Ivan, C.
Barbarotto, E.
De, Vries I.
Zhang, X.
Ferracin, M.
Churchman, M.
Van Galen, J. F.
Beverloo, B. H.
Shariati, M.
Haderk, F.
Estecio, M. R.
Garcia-Manero, G.
Patijn, G.A.
Gotley, D.C.
Bhardwaj, V.
Shureiqi, I.
Sen, S.
Multani, A. S.
Welsh, J.
Yamamoto, K.
Taniguchi, I.
Song, M.-A.
Gallinger, S.
Casey, G.
Thibodeau, S.N.
Le Marchand, L.
Tiirikainen, M.
Mani, S.A.
Zhang, W.
Davuluri, R.V.
Mimori, K.
Mori, M.
Sieuwerts, A.M.
Martens, J.W.M.
Tomlinson, I.
Negrini, M.
Berindan-Neagoe, I.
Foekens, J.A.
Hamilton, S.R.
Lanza, G.
Kopetz, S.
Fodde, R.
Calin, G.A.
Title CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer
Journal name Genome Research   Check publisher's open access policy
ISSN 1088-9051
Publication date 2013-01-01
Sub-type Article (original research)
DOI 10.1101/gr.152942.112
Open Access Status File (Publisher version)
Volume 23
Issue 9
Start page 1446
End page 1461
Total pages 16
Place of publication Cold Spring Harbor, NY 11724 United States
Publisher Cold Spring Harbor Laboratory Press
Language eng
Abstract 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 226 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 11 Apr 2014, 02:54:20 EST by Matthew Lamb on behalf of School of Medicine