H3K27me3 loss plays a vital role in CEMIP mediated carcinogenesis and progression of breast cancer with poor prognosis

Abstract Background H3K27me3 modification inactivates gene transcription by resulting in condensed chromatin. However, the landscape and biological functions of H3K27me3 in breast cancer remain unclear. Methods Fluorescence enzyme assay was used to analyze the cell proliferation. Transwell assay was used to test the ability of migration and invasion in MDA-MB-231 cells with designed treatment. Transfection of exogenous plasmid was used to intervene specific gene expression. Nude mouse tumor xenograft model was employed to detect the effect of GSKJ-4 in vivo. ChIP-Seq analyzed the modification state of H3K27me3 around the TSS of the gene CEMIP. RNA-Seq was used to analyze the mRNA levels after treating with GSKJ-4 in MDA-MB-231 cells. Results Loss of H3K27me3 is specific for aggressive subtypes of breast cancer and may be a useful diagnostic marker. Epigenetic chemical screening identified histone H3K27me3 demethylation inhibition as a therapeutic strategy for triple-negative breast cancer (TNBC). Functional studies and RNA-seq/ChIP-seq data revealed that inactivation of the protein CEMIP (which is translated by oncogene KIAA1199) by increasing H3K27me3 leads to decreased tumor cell growth and migration. Moreover, survival analysis showed that CEMIP was associated with poor outcome in TNBC. Conclusions Our data suggest H3K27me3 loss as an important event in CEMIP mediated breast cancer carcinogenesis and progression. Loss of H3K27me3 is specific for aggressive subtypes of breast cancer and may be a useful diagnostic marker.