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Mol. Cells

Published online June 24, 2022

© The Korean Society for Molecular and Cellular Biology

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

Kwangho Kim1,3,4 , Tae Young Ryu1,4 , Jinkwon Lee1,2 , Mi-Young Son1,2 , Dae-Soo Kim1,2 , Sang Kyum Kim3,* , and Hyun-Soo Cho1,2,*

1Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea, 2Department of Functional Genomics, Korea University of Science and Technology, Daejeon 34113, Korea, 3College of Pharmacy, Chungnam National University, Daejeon 34134, Korea, 4These authors contributed equally to this work.

Correspondence to : chohs@kribb.re.kr(HSC); sangkim@cnu.ac.kr(SKK)

Received: January 21, 2022; Revised: April 26, 2022; Accepted: April 26, 2022

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.

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 apoptosis, C/EBP homologous protein, colorectal cancer, Euchromatic histone-lysine N-methyltransferase 1

Article

On-line First

Mol. Cells

Published online June 24, 2022

Copyright © The Korean Society for Molecular and Cellular Biology.

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

Kwangho Kim1,3,4 , Tae Young Ryu1,4 , Jinkwon Lee1,2 , Mi-Young Son1,2 , Dae-Soo Kim1,2 , Sang Kyum Kim3,* , and Hyun-Soo Cho1,2,*

1Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea, 2Department of Functional Genomics, Korea University of Science and Technology, Daejeon 34113, Korea, 3College of Pharmacy, Chungnam National University, Daejeon 34134, Korea, 4These authors contributed equally to this work.

Correspondence to:chohs@kribb.re.kr(HSC); sangkim@cnu.ac.kr(SKK)

Received: January 21, 2022; Revised: April 26, 2022; Accepted: April 26, 2022

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.

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: apoptosis, C/EBP homologous protein, colorectal cancer, Euchromatic histone-lysine N-methyltransferase 1

Mol. Cells
Aug 31, 2022 Vol.45 No.8, pp. 513~602
COVER PICTURE
Cryo-EM structure of human porphyrin transporter ABCB6 (main figure) shows that binding of hemin (inset, magenta) in concert with two glutathione molecules (cyan) primes ABCB6 for high ATP turnover (Kim et al., pp. 575-587).

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