CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer.
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 tum...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2013
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| _version_ | 1797077684073791488 |
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| author | Ling, H Spizzo, R Atlasi, Y Nicoloso, M Shimizu, M Redis, R Nishida, N Gafà, R Song, J Guo, Z Ivan, C Barbarotto, E De Vries, I Zhang, X Ferracin, M Churchman, M van Galen, J Beverloo, B Shariati, M Haderk, F Estecio, MR Garcia-Manero, G Patijn, G Gotley, D Bhardwaj, V |
| author_facet | Ling, H Spizzo, R Atlasi, Y Nicoloso, M Shimizu, M Redis, R Nishida, N Gafà, R Song, J Guo, Z Ivan, C Barbarotto, E De Vries, I Zhang, X Ferracin, M Churchman, M van Galen, J Beverloo, B Shariati, M Haderk, F Estecio, MR Garcia-Manero, G Patijn, G Gotley, D Bhardwaj, V |
| author_sort | Ling, H |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T00:21:30Z |
| format | Journal article |
| id | oxford-uuid:7cb386a5-6a16-4387-94dc-e273a8d69703 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:21:30Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:7cb386a5-6a16-4387-94dc-e273a8d697032022-03-26T20:58:51ZCCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7cb386a5-6a16-4387-94dc-e273a8d69703EnglishSymplectic Elements at Oxford2013Ling, HSpizzo, RAtlasi, YNicoloso, MShimizu, MRedis, RNishida, NGafà, RSong, JGuo, ZIvan, CBarbarotto, EDe Vries, IZhang, XFerracin, MChurchman, Mvan Galen, JBeverloo, BShariati, MHaderk, FEstecio, MRGarcia-Manero, GPatijn, GGotley, DBhardwaj, VThe 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. |
| spellingShingle | Ling, H Spizzo, R Atlasi, Y Nicoloso, M Shimizu, M Redis, R Nishida, N Gafà, R Song, J Guo, Z Ivan, C Barbarotto, E De Vries, I Zhang, X Ferracin, M Churchman, M van Galen, J Beverloo, B Shariati, M Haderk, F Estecio, MR Garcia-Manero, G Patijn, G Gotley, D Bhardwaj, V CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. |
| title | CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. |
| title_full | CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. |
| title_fullStr | CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. |
| title_full_unstemmed | CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. |
| title_short | CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. |
| title_sort | ccat2 a novel noncoding rna mapping to 8q24 underlies metastatic progression and chromosomal instability in colon cancer |
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