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 (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.
Original language | Undefined/Unknown |
---|---|
Pages (from-to) | 1446-1461 |
Number of pages | 16 |
Journal | Genome Research |
Volume | 23 |
Issue number | 9 |
DOIs | |
Publication status | Published - 2013 |
Research programs
- EMC MM-03-24-01
- EMC MM-03-86-01