NUDT7 Loss Promotes KrasG12D CRC Development

Cancers
Jinsoo SongEun-Jung Jin

Abstract

Studies have suggested that dysregulation of peroxisomal lipid metabolism might play an important role in colorectal cancer (CRC) development. Here, we found that KrasG12D-driven CRC tumors demonstrate dysfunctional peroxisomal b-oxidation and identified Nudt7 (peroxisomal coenzyme A diphosphatase NUDT7) as one of responsible peroxisomal genes. In KrasG12D-driven CRC tumors, the expression level of Nudt7 was significantly decreased. Treatment of azoxymethane/dextran sulfate sodium (AOM/DSS) into Nudt7 knockout (Nudt7-/-) mice significantly induced lipid accumulation and the expression levels of CRC-related genes whereas xenografting of Nudt7-overexpressed LS-174T cells into mice significantly reduced lipid accumulation and the expression levels of CRC-related genes. Ingenuity pathway analysis of microarray using the colon of Nudt7-/- and Nudt7+/+ mice treated with AOM/DSS suggested Wnt signaling as one of activated signaling pathways in Nudt7-/- colons. Upregulated levels of β-catenin were observed in the colons of KrasG12D and AOM/DSS-treated Nudt7-/- mice and downstream targets of β-catenin such as Myc, Ccdn1, and Nos2, were also significantly increased in the colon of Nudt7-/- mice. We observed an increased level of palmitic...Continue Reading

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Citations

Mar 7, 2021·International Journal of Molecular Sciences·Roni H G Wright, Miguel Beato

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Datasets Mentioned

BETA
GSE41258
GSE12398

Methods Mentioned

BETA
GTPase
xenograft
Profiler
Protein Assay

Software Mentioned

GraphPad Prism
Affymetrix GeneChip Command Console
Image J
PermutMatrix
IHC Profiler

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