Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Epigenetic Silencing of CHOP Expression by the Histone Methyltransferase EHMT1 Regulates Apoptosis in Colorectal Cancer Cells

  • Kim, Kwangho (Korea Research Institute of Bioscience and Biotechnology) ;
  • Ryu, Tae Young (Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Jinkwon (Korea Research Institute of Bioscience and Biotechnology) ;
  • Son, Mi-Young (Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Dae-Soo (Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Sang Kyum (College of Pharmacy, Chungnam National University) ;
  • Cho, Hyun-Soo (Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2022.01.21
  • Accepted : 2022.04.26
  • Published : 2022.09.30
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Abstract

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.

Keywords

Acknowledgement

This work was supported by a grant from the Technology Innovation Program (No. 20008777) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea), a National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, ICT, and Future Planning (NRF-2020R1A2B5B01002028, NRF-2018M3A9H3023077/NRF-2021M3A9H3016046), a Korean Fund for Regenerative Medicine (KFRM) grant funded by the Korean government (the Ministry of Science and ICT, the Ministry of Health & Welfare, 21A0404L1), and the KRIBB Research Initiative Program. The funders had no role in the study design, data collection or analysis, decision to publish, or preparation of the manuscript.

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