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Overexpression of KRAS-Q25A mutant with enhanced GTPase activity inhibits the progression of KRAS-G12D colorectal cancer

GSE332549 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2026/05/21 Platform GPL24247
Summary
The high mutation rate of KRAS in cancers leads to consistent activation of downstream signaling and eventually promoting malignancy. While restoring GTP hydrolysis in KRAS-mutant tumors represents a promising therapeutic strategy, its mechanistic basis remains unclear. Our previous finding that mutation of the KRAS P4 pocket exhibited elevated intrinsic GTPase activity of KRAS, and therefore presented a promising new strategy to intervene KRAS mutated cancer. This exciting potential has now been verified in the current work. We explored how P4 mutants impact the progression of colorectal cancer, and found KRAS-Q25A, a P4 mutant with the most significant elevated GTPase activity, can inhibit the progression of CT26 cell, a commonly used colorectal cell line with KRAS-G12D mutation. Moreover, this inhibitory effect of KRAS-Q25A is depended on its GTP hydrolysis process. To assess the impact of KRAS-Q25A overexpression on the overall cellular state, we performed RNA sequencing on CT26 cells overexpressing either KRAS-WT or KRAS-Q25A.
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Also filed as BioProject PRJNA1468596 and SRA study SRP702343. Searching any of these in the dataset finder brings you back here.

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