Epigenetic alterations of TP53INP1 by EHMT2 regulate the cell cycle in gastric cancer.

Autor: Ryu TY; Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea., Tae IH; Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea., Han TS; Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea.; Korea University of Science and Technology, Daejeon, 34316, Republic of Korea.; Chungnam National University College of Medicine, Daejeon, 35015, Republic of Korea., Lee J; Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea.; Korea University of Science and Technology, Daejeon, 34316, Republic of Korea., Kim K; Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea., Kang Y; Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea.; Korea University of Science and Technology, Daejeon, 34316, Republic of Korea., Kim S; Chungnam National University College of Medicine, Daejeon, 35015, Republic of Korea., Lee HJ; Chungnam National University College of Medicine, Daejeon, 35015, Republic of Korea., Jung CR; Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea.; Korea University of Science and Technology, Daejeon, 34316, Republic of Korea., Lim JH; Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea.; Korea University of Science and Technology, Daejeon, 34316, Republic of Korea., Kim DS; Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea. kds2465@kribb.re.kr.; Korea University of Science and Technology, Daejeon, 34316, Republic of Korea. kds2465@kribb.re.kr., Son MY; Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea. myson@kribb.re.kr.; Korea University of Science and Technology, Daejeon, 34316, Republic of Korea. myson@kribb.re.kr.; Department of Biological Science, Sungkyunkwan University, Suwon, 16419, Republic of Korea. myson@kribb.re.kr., Cho HS; Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea. chohs@kribb.re.kr.; Korea University of Science and Technology, Daejeon, 34316, Republic of Korea. chohs@kribb.re.kr.; Department of Biological Science, Sungkyunkwan University, Suwon, 16419, Republic of Korea. chohs@kribb.re.kr.
Jazyk: angličtina
Zdroj: Experimental hematology & oncology [Exp Hematol Oncol] 2024 Aug 19; Vol. 13 (1), pp. 86. Date of Electronic Publication: 2024 Aug 19.
DOI: 10.1186/s40164-024-00554-y
Abstrakt: Background: Gastric cancer (GC) is a type of cancer with high incidence and mortality rates. Although various chemical interventions are being developed to treat gastric cancer, there is a constant demand for research into new GC treatment targets and modes of action (MOAs) because of the low effectiveness and side effects of current treatments.
Methods: Using the TCGA data portal, we identified EHMT2 overexpression in GC samples. Using RNA-seq and EHMT2-specific siRNA, we investigated the role of EHMT2 in GC cell proliferation and validated its function with two EHMT2-specific inhibitors. Through the application of 3D spheroid culture, patient-derived gastric cancer organoids (PDOs), and an in vivo model, we confirmed the role of EHMT2 in GC cell proliferation.
Results: In this study, we found that EHMT2, a histone 3 lysine 9 (H3K9) methyltransferase, is significantly overexpressed in GC patients compared with healthy individuals. Knockdown of EHMT2 with siRNA induced G1 cell cycle arrest and attenuated GC cell proliferation. Furthermore, we confirmed that TP53INP1 induction by EHMT2 knockdown induced cell cycle arrest and inhibited GC cell proliferation. Moreover, specific EHMT2 inhibitors, BIX01294 and UNC0638, induced cell cycle arrest in GC cell lines through TP53INP1 upregulation. The efficacy of EHMT2 inhibition was further confirmed in a 3D spheroid culture system, PDOs, and a xenograft model.
Conclusions: Our findings suggest that EHMT2 is an attractive therapeutic target for GC treatment.
(© 2024. The Author(s).)
Databáze: MEDLINE
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