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

By H. Ling, R. Spizzo, Y. Atlasi, M. Nicoloso, M. Shimizu, R. Redis, N. Nishida, R. Gafà, J. Song, Z. Guo and 43 more. Genome Research, 2013

620 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Molecular Biology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/4550c8a8c91653899480d4220a674ec46da5a8c7

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Citations in the corpus

Non-coding RNAs in disease: from mechanisms to therapeutics (2023, positive): “MALAT1 has been identified as an early prognostic marker for metastasis development in surgically removed lung cancer 233 , whereas CCAT1 and CCAT2 have well-characterized mechanistic roles and serve as prognostic biomarkers for colorectal cancer 234,235 .”
Comprehensive Genomic Characterization of Long Non-Coding RNAs across Human Cancers (2015, background): “In addition to the fact that they are highly deregulated in tumors (Akrami et al., 2013; Calin et al., 2007; Du et al., 2013; Iyer et al., 2015; Kim et al., 2014; Li et al., 2015; Ling et al., 2013; Prensner et al., 2011; Trimarchi et al., 2014; Xing et al., 2014), lncRNAs have been found to act as ”
Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer (2017, background): “4 Overexpression SNP rs6983267 Upregulation of MYC and enhancement of WNT signalling pathway through TCF7L2 Induction of cell proliferation, invasion and chromosomal instability [98]”
Long Non-Coding RNA in the Pathogenesis of Cancers (2019, background): “between CCAT2 and transcription factor 7 like 2 (TCF7L2), resulting in increased transcriptional activity of MYC proto-oncogene and then enhancing the activity of the Wnt signaling pathway [291].”