Synthetic Reader-Actuators Targeted to Polycomb-Silenced Genes Block Triple-Negative Breast Cancer Proliferation and Invasion.

ABSTRACT: Scientists have used pharmacological inhibitors of polycomb proteins to restore the expression of tumor suppressor genes and stop cancer proliferation and invasion. A major limitation of this approach is that key transcriptional activators, such as TP53 and BAF SWI/SNF, are often mutated in cancer. Poor clinical results for polycomb-targeting therapies in solid cancers, including triple-negative breast cancer (TNBC), could discourage the further development of epigenetic monotherapies. Here, we performed epigenome actuation with a synthetic reader-actuator (SRA) that binds trimethylated histone H3 lysine 27 in polycomb chromatin and modulates core transcriptional activators. In SRA-expressing TNBC BT-549 cells, 122 genes become upregulated ≥2-fold, including the genes involved in cell deat

SUBMITTER: Hong L 

PROVIDER: S-EPMC10623628 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature