SurgeryAug 11, 2007

A specific mutation in the CDK2-AP1 gene reduces its mRNA stability and lowers gene expression in a type of colorectal cancer with unstable DNA

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 20, 2026

Abstract

Mutant sequences of the CDK2-AP1 gene resulted in significantly reduced expression of a green fluorescent protein compared to wild-type sequences.

Decreased expression of CDK2-AP1 in colorectal cancer is linked to deletion mutations in the poly (T) 8 repeat sequence of its 3'-UTR.
The mutant 3'-UTR resulted in lower stability of CDK2-AP1 mRNA compared to the wild-type.
Both fluorescent and quantitative PCR assays confirmed the reduced expression of the GFP gene linked to the mutant 3'-UTR.
Findings suggest that reduced mRNA stability is a mechanism contributing to decreased CDK2-AP1 expression in human colorectal cancer.

Simplified

BACKGROUND: We have previously published results indicating that decreased expression of CDK2-AP1 in MSI human colorectal cancer is associated with deletion mutations in the poly (T) 8 repeat sequence within the 3'-UTR of the CDK2-AP1 gene. In this study, we test the hypothesis that the del T mutation results in decreased CDK2-AP1 expression by causing reduced mRNA stability.

METHODS: We introduced wild-type and mutant 3'-UTR sequences fused to a green fluorescent protein (GFP) gene separately into human CRC cell lines and quantified the expression of the GFP gene. Native CDK2-AP1 mRNA stability was measured in human CRC cell lines, using an actinomycin D assay and the mRNA structure folding software mfold 3.2.

RESULTS: Mutant GFP-3'-UTR samples demonstrated significantly reduced GFP expression compared with wild-type GFP-3'-UTR as measured by both FACS and real-time PCR. Both the actinomycin D assay and mfold software demonstrated significantly reduced mRNA stability for the del T poly (T) 8 transcript compared with the wild type.

CONCLUSIONS: In summary, these novel results support our hypotheses that the del T poly (T) 8 observed in the 3'-UTR of the CDK2-AP1 gene in human MSI CRC is functionally significant and results in decreased CDK2-AP1 expression. The results also indicate the mechanism of this decreased expression is caused at least in part by decreased mRNA stability.

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A specific mutation in the CDK2-AP1 gene reduces its mRNA stability and lowers gene expression in a type of colorectal cancer with unstable DNA

Abstract

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