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 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

Prequalification: using systems to problem dissolve

The requirement to prequalify prior to tendering for a project is often reported as burdensome. We need more ways to think constructively about this sort of project management problem. The pragmatists argue that constructive thinking includes encouraging stakeholders to shift from their default conception of a problematic situation. Ackoff (2006) suggested a way of doing this. He called it “problem dissolving.” This includes “zooming out” from the situation to conceive of the old problem situation as just one element in a metasystem. This article explains how and why problem dissolving might be used to reconceptualize prequalification. After ex-plaining the approach, it tests the approach on industry experts. Projects are human activity systems, so it seemed reasonable to reflect on prequalification using the attributes of a project as a system: purpose, transformation, connectivity, and boundary. A reconceptualization of prequalification emerged where it was seen to have the potential to become a policy mechanism for improving the industry.Bassam Baroudi, Mike Metcalf