Epigenetic Silencing of CHOP Expression by the Histone Methyltransferase EHMT1 Regulates Apoptosis in Colorectal Cancer Cells.

Autor: Kim K; Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea.; College of Pharmacy, Chungnam National University, Daejeon 34134, Korea.; These authors contributed equally to this work., Ryu TY; Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea.; These authors contributed equally to this work., Lee J; Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea.; Department of Functional Genomics, Korea University of Science and Technology, Daejeon 34113, Korea., Son MY; Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea.; Department of Functional Genomics, Korea University of Science and Technology, Daejeon 34113, Korea., Kim DS; Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea.; Department of Functional Genomics, Korea University of Science and Technology, Daejeon 34113, Korea., Kim SK; College of Pharmacy, Chungnam National University, Daejeon 34134, Korea., Cho HS; Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea.; Department of Functional Genomics, Korea University of Science and Technology, Daejeon 34113, Korea.
Jazyk: angličtina
Zdroj: Molecules and cells [Mol Cells] 2022 Sep 30; Vol. 45 (9), pp. 622-630. Date of Electronic Publication: 2022 Jun 24.
DOI: 10.14348/molcells.2022.0014
Abstrakt: Colorectal cancer (CRC) has a high mortality rate among cancers worldwide. To reduce this mortality rate, chemotherapy (5-fluorouracil, oxaliplatin, and irinotecan) or targeted therapy (bevacizumab, cetuximab, and panitumumab) has been used to treat CRC. However, due to various side effects and poor responses to CRC treatment, novel therapeutic targets for drug development are needed. In this study, we identified the overexpression of EHMT1 in CRC using RNA sequencing (RNA-seq) data derived from TCGA, and we observed that knocking down EHMT1 expression suppressed cell growth by inducing cell apoptosis in CRC cell lines. In Gene Ontology (GO) term analysis using RNA-seq data, apoptosis-related terms were enriched after EHMT1 knockdown. Moreover, we identified the CHOP gene as a direct target of EHMT1 using a ChIP (chromatin immunoprecipitation) assay with an anti-histone 3 lysine 9 dimethylation (H3K9me2) antibody. Finally, after cotransfection with siEHMT1 and siCHOP, we again confirmed that CHOP-mediated cell apoptosis was induced by EHMT1 knockdown. Our findings reveal that EHMT1 plays a key role in regulating CRC cell apoptosis, suggesting that EHMT1 may be a therapeutic target for the development of cancer inhibitors.
Databáze: MEDLINE