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Analysis of transcriptional changes associated to proteasome inhibition in HCT-116 human colorectal cancer cells

ABSTRACT: The proteasome is a central player in several cellular aspects, such as homeostasis, cell cycle progression, and even transcription. Recent work has shown that proteasome inhibition promotes pervasive epigenetic changes in the human genome. However, the impact of proteasome inhibitors on ncRNAs is poorly understood. We treated control (asynchronous) or G2-synchronized HCT-116 human colon cancer cells with the proteasome inhibitors MG132 and bortezomib and performed total RNA-seq. We also included cells treated simultaneously with MG132 and the RNA-pol II inhibitor α-amanitin to determine the transcriptional changes mediated by such RNA polymerase. We report that MG132 and bortezomib impact similar regions of the genome. A remarkable transcriptional activation was observed in centromeres and pericentromers, especially in α-satellite repeats. RNAs emanating from these regions are known to participate in chromosome segregation. Our results suggest that the proteasome can regulate mitotic progression, not only by participating in protein turnover, but also by regulating ncRNAs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE165325 | GEO | 2021/12/14

REPOSITORIES: GEO

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