한빛사논문
- 조회1,007
Tae Young Ryu1,2,7, Kwangho Kim1,7, Tae-Su Han1,7, Mi-Ok Lee1,3, Jinkwon Lee1,3, Jinhyeon Choi1, Kwang Bo Jung1, Eun-Jeong Jeong1, Da Mi An1, Cho-Rok Jung1,3, Jung Hwa Lim1, Jaeeun Jung1, Kunhyang Park1, Moo-Seung Lee1,3, Mi-Young Kim2, Soo Jin Oh4, Keun Hur5, Ryuji Hamamoto6, Doo-Sang Park1,3,*, Dae-Soo Kim1,3,*, Mi-Young Son1,3,* and Hyun-Soo Cho1,3,*
1Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea. 2Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea. 3Korea University of Science and Technology, Daejeon 34113, Republic of Korea. 4Asan Institute for Life Sciences, Asan Medical Center and Department of Convergence Medicine, College of Medicine, University of Ulsan, Seoul 05505, Republic of Korea. 5Department of Biochemistry and Cell biology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea. 6Division of Molecular Modification and Cancer Biology, National Cancer Center, Tokyo 104-0045, Japan. 7These authors contributed equally: Tae Young Ryu, Kwangho Kim, Tae-Su Han.
*Corresponding author.
Abstract
The human microbiome plays an essential role in the human immune system, food digestion, and protection from harmful bacteria by colonizing the human intestine. Recently, although the human microbiome affects colorectal cancer (CRC) treatment, the mode of action between the microbiome and CRC remains unclear. This study showed that propionate suppressed CRC growth by promoting the proteasomal degradation of euchromatic histone-lysine N-methyltransferase 2 (EHMT2) through HECT domain E3 ubiquitin protein ligase 2 (HECTD2) upregulation. In addition, EHMT2 downregulation reduced the H3K9me2 level on the promoter region of tumor necrosis factor α-induced protein 1 (TNFAIP1) as a novel direct target of EHMT2. Subsequently, TNFAIP1 upregulation induced the apoptosis of CRC cells. Furthermore, using Bacteroides thetaiotaomicron culture medium, we confirmed EHMT2 downregulation via upregulation of HECTD2 and TNFAIP1 upregulation. Finally, we observed the synergistic effect of propionate and an EHMT2 inhibitor (BIX01294) in 3D spheroid culture models. Thus, we suggest the anticancer effects of propionate and EHMT2 as therapeutic targets for colon cancer treatment and may provide the possibility for the synergistic effects of an EHMT2 inhibitor and microbiome in CRC treatment.
논문정보
- Research article
- 2022년 01월 (BRIC 등록일 2022-01-11)
- 국내(교신)+국외 연구진
- 생명과학 > 노화/암생물학
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