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Omics · study · 2026

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

Listed in NCBI GEO

The high mutation rate of KRAS in cancers leads to consistent activation of downstream signaling and eventually promoting malignancy.

Description

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.

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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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From keywords
Life Sciences
Inferred from text
Cancer 75% · RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 10 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE33254913 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:cancerenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title