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Proteasome inhibition induces alteration of DNA methylation profile by attenuating the synthesis of DNA methyltransferase 1 and 3B in colorectal cancer

GSE268199 Homo sapiens Expression profiling by high throughput sequencing 9 samples Submitted 2025/02/27 Platform GPL29480
Summary
Proteasome is an essential organelle in guarding cellular protein homeostasis. Here, we report that inhibition of proteasome alters the profile of DNA methylation in colorectal cancer (CRC) by blocking the synthesis of DNA methyltransferases (DNMTs). We found that treating CRC cells with proteasome inhibitors (PIs) suppress the translation of DNMT1 and DNMT3B by inactivating AKT and mammalian target of rapamycin (mTOR), dependent on the accumulation of p300, an acetyltransferase inactivating AKT by mediating its acetylation modification. Furthermore, we demonstrated downregulation of DNMT1 and DNMT3B protects cancer cells against PI treatment, potentially by reprogramming the transcriptome of CRC cells; highlighting the key role of DNMTs in response to proteostasis disturbance
Published in
Proteasome inhibition induces DNA methylation alteration by attenuating the synthesis of DNA methyltransferase 1 and 3B in colorectal cancer
Zhou W, Sheng Y, Hu D et al. · Scientific reports 2025 · PMID 40075132 · doi:10.1038/s41598-025-92390-1
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Also filed as BioProject PRJNA1115106 and SRA study SRP509420. Searching any of these in the dataset finder brings you back here.

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