CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer
| العنوان: | CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer |
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| المؤلفون: | Jian Song, David C. Gotley, Naohiro Nishida, Stephen N. Thibodeau, Gijs A. Patijn, Ingrid de Vries, Mike Churchman, Roxana S. Redis, Ken Yamamoto, Ramana V. Davuluri, Itsuki Taniguchi, Berna Beverloo, Maarit Tiirikainen, Imad Shureiqi, Xinna Zhang, Anieta M. Sieuwerts, Roberta Gafà, Graham Casey, Stanley R. Hamilton, James W. Welsh, Masaki Mori, Massimo Negrini, Franziska Haderk, Janneke F. van Galen, Koshi Mimori, Riccardo Spizzo, Milena S. Nicoloso, Cristina Ivan, Marcos R. Estecio, Steven Gallinger, Riccardo Fodde, Ian Tomlinson, Loic Le Marchand, Vikas Bhardwaj, Min-Ae Song, Sendurai A. Mani, George A. Calin, Wei Zhang, Guillermo Garcia-Manero, Asha S. Multani, Manuela Ferracin, Hui Ling, Ioana Berindan-Neagoe, Yaser Atlasi, Masayoshi Shimizu, Subrata Sen, Giovanni Lanza, Zhiyi Guo, Maryam Shariati, Elisa Barbarotto, John A. Foekens, John W.M. Martens, Scott Kopetz |
| المساهمون: | Pathology, Clinical Genetics, Medical Oncology, H. Ling, R. Spizzo, Y. Atlasi, M. Nicoloso, M. Shimizu, R. S. Redi, N. Nishida, R. Gafa, J. Song, Z. Guo, C. Ivan, E. Barbarotto, I. De Vrie, X. Zhang, M. Ferracin, M. Churchman, J. F. van Galen, B. H. Beverloo, M. Shariati, F. Haderk, M. R. Estecio, G. Garcia-Manero, G. A. Patijn, D. C. Gotley, V. Bhardwaj, I. Shureiqi, S. Sen, A. S. Multani, J. Welsh, K. Yamamoto, I. Taniguchi, M.-A. Song, S. Gallinger, G. Casey, S. N. Thibodeau, L. Le Marchand, M. Tiirikainen, S. A. Mani, W. Zhang, R. V. Davuluri, K. Mimori, M. Mori, A. M. Sieuwert, J. W. M. Marten, I. Tomlinson, M. Negrini, I. Berindan-Neagoe, J. A. Foeken, S. R. Hamilton, G. Lanza, S. Kopetz, R. Fodde, G. A. Calin |
| المصدر: | Genome Research, 23(9), 1446-1461. Cold Spring Harbor Laboratory Press |
| بيانات النشر: | Cold Spring Harbor Laboratory Press, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, Transcription, Genetic, Colorectal cancer, Transcription Factor 7-Like 1 Protein, SNP RS6983267, BETA-CATENIN, COLORECTAL-CANCER, Metastasis, Mice, 0302 clinical medicine, Chromosome instability, Transcriptional regulation, TRANSCRIPTION, Neoplasm Metastasis, Wnt Signaling Pathway, Genetics (clinical), Genetics, Regulation of gene expression, 0303 health sciences, Wnt signaling pathway, Non-coding RNA, 3. Good health, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Colonic Neoplasms, Female, RNA, Long Noncoding, Chromosomes, Human, Pair 8, colorectal cancer, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, NO, target, Proto-Oncogene Proteins c-myc, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Cell Line, Tumor, Chromosomal Instability, microRNA, expression, C-MYC, medicine, BREAST-CANCER, Animals, Humans, 030304 developmental biology, HUMAN-CELLS, Research, medicine.disease, APC, MicroRNAs, Case-Control Studies, Cancer research, protein, colorectal cancer, expression, microRNas, protein, target |
| الوصف: | 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. |
| وصف الملف: | application/pdf; STAMPA |
| تدمد: | 1549-5469 1088-9051 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::402d8f59130ed598eb476b9ade60ec23Test https://doi.org/10.1101/gr.152942.112Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....402d8f59130ed598eb476b9ade60ec23 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15495469 10889051 |
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