Mol. Cells
Published online March 10, 2023
© The Korean Society for Molecular and Cellular Biology
Correspondence to : mirang@kribb.re.kr
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/.
Gastric cancer (GC) is a complex disease influenced by multiple genetic and epigenetic factors. Chronic inflammation caused by Helicobacter pylori infection and dietary risk factors can result in the accumulation of aberrant DNA methylation in gastric mucosa, which promotes GC development. Tensin 4 (TNS4), a member of the Tensin family of proteins, is localized to focal adhesion sites, which connect the extracellular matrix and cytoskeletal network. We identified upregulation of TNS4 in GC using quantitative reverse transcription PCR with 174 paired samples of GC tumors and adjacent normal tissues. Transcriptional activation of TNS4 occurred even during the early stage of tumor development. TNS4 depletion in GC cell lines that expressed high to moderate levels of TNS4, i.e., SNU-601, KATO III, and MKN74, reduced cell proliferation and migration, whereas ectopic expression of TNS4 in those lines that expressed lower levels of TNS4, i.e., SNU-638, MKN1, and MKN45 increased colony formation and cell migration. The promoter region of TNS4 was hypomethylated in GC cell lines that showed upregulation of TNS4. We also found a significant negative correlation between TNS4 expression and CpG methylation in 250 GC tumors based on The Cancer Genome Atlas (TCGA) data. This study elucidates the epigenetic mechanism of TNS4 activation and functional roles of TNS4 in GC development and progression and suggests a possible approach for future GC treatments.
Keywords cell migration, cell proliferation, DNA methylation, gastric cancer, TNS4
Mol. Cells
Published online March 10, 2023
Copyright © The Korean Society for Molecular and Cellular Biology.
Haejeong Heo1,2 , Hee-Jin Kim1
, Keeok Haam1
, Hyun Ahm Sohn1
, Yang-Ji Shin1,2
, Hanyong Go1,2
, Hyo-Jung Jung1
, Jong-Hwan Kim3
, Sang-Il Lee4
, Kyu-Sang Song5
, Min-Ju Kim6
, Haeseung Lee6
, Eun-Soo Kwon1,7
, Seon-Young Kim2,3
, Yong Sung Kim8,9
, and Mirang Kim1,2,9,*
1Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea, 2Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon 34113, Korea, 3Korea Bioinformation Center, KRIBB, Daejeon 34141, Korea, 4Department of Surgery, College of Medicine, Chungnam National University, Daejeon 35015, Korea, 5Department of Pathology, College of Medicine, Chungnam National University, Daejeon 35015, Korea, 6Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Korea, 7Department of Biomolecular Science, KRIBB School of Bioscience, UST, Daejeon 34113, Korea, 8Functional Genomics Institute, PDXen Biosystems Co., Daejeon 34129, Korea, 9Personalized Genomic Medicine Research Center, KRIBB, Daejeon 34141, Korea
*Corresponde
Correspondence to:mirang@kribb.re.kr
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/.
Gastric cancer (GC) is a complex disease influenced by multiple genetic and epigenetic factors. Chronic inflammation caused by Helicobacter pylori infection and dietary risk factors can result in the accumulation of aberrant DNA methylation in gastric mucosa, which promotes GC development. Tensin 4 (TNS4), a member of the Tensin family of proteins, is localized to focal adhesion sites, which connect the extracellular matrix and cytoskeletal network. We identified upregulation of TNS4 in GC using quantitative reverse transcription PCR with 174 paired samples of GC tumors and adjacent normal tissues. Transcriptional activation of TNS4 occurred even during the early stage of tumor development. TNS4 depletion in GC cell lines that expressed high to moderate levels of TNS4, i.e., SNU-601, KATO III, and MKN74, reduced cell proliferation and migration, whereas ectopic expression of TNS4 in those lines that expressed lower levels of TNS4, i.e., SNU-638, MKN1, and MKN45 increased colony formation and cell migration. The promoter region of TNS4 was hypomethylated in GC cell lines that showed upregulation of TNS4. We also found a significant negative correlation between TNS4 expression and CpG methylation in 250 GC tumors based on The Cancer Genome Atlas (TCGA) data. This study elucidates the epigenetic mechanism of TNS4 activation and functional roles of TNS4 in GC development and progression and suggests a possible approach for future GC treatments.
Keywords: cell migration, cell proliferation, DNA methylation, gastric cancer, TNS4
Hao Wang, Xiang-Long Duan, Xiao-Li Qi, Lei Meng, Yi-Song Xu, Tong Wu, and Peng-Gao Dai
Mol. Cells 2017; 40(1): 45-53 https://doi.org/10.14348/molcells.2017.2245Uijin Kim and Dong-Sung Lee
Mol. Cells 2023; 46(2): 86-98 https://doi.org/10.14348/molcells.2023.0013Sangrea Shim, Hong Gil Lee, and Pil Joon Seo
Mol. Cells 2021; 44(10): 746-757 https://doi.org/10.14348/molcells.2021.0160