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

ABSTRACT: Proteasome is an essential organelle responsible for maintaining cellular protein homeostasis, but its relationship with DNA methylation remains unknown. In this study, we assessed DNA methylation of colorectal cancer (CRC) cells following treatment with proteasome inhibitors, and investigated the underlying mechanism of DNA methylation changes and the biological effects on CRC cells. We established that inhibition of proteasome leads to significant alterations in DNA methylation profile in CRC by suppressing the synthesis of DNA methyltransferases (DNMTs). We found that treating CRC cells with proteasome inhibitors results in attenuated translation of DNMT1 and DNMT3B, mediated by the inactivation of AKT and mammalian target of rapamycin (mTOR), which is dependent on the accumulation of p

SUBMITTER: Zhou W 

PROVIDER: S-EPMC11903776 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature