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Mol. Cells

Published online March 10, 2023

© The Korean Society for Molecular and Cellular Biology

Epigenetic Activation of Tensin 4 Promotes Gastric Cancer Progression

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

Received: September 19, 2022; Revised: December 18, 2022; Accepted: December 18, 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

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

Article

On-line First

Mol. Cells

Published online March 10, 2023

Copyright © The Korean Society for Molecular and Cellular Biology.

Epigenetic Activation of Tensin 4 Promotes Gastric Cancer Progression

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

Received: September 19, 2022; Revised: December 18, 2022; Accepted: December 18, 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

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
Feb 28, 2023 Vol.46 No.2, pp. 69~129
COVER PICTURE
The bulk tissue is a heterogeneous mixture of various cell types, which is depicted as a skein of intertwined threads with diverse colors each of which represents a unique cell type. Single-cell omics analysis untangles efficiently the skein according to the color by providing information of molecules at individual cells and interpretation of such information based on different cell types. The molecules that can be profiled at the individual cell by single-cell omics analysis includes DNA (bottom middle), RNA (bottom right), and protein (bottom left). This special issue reviews single-cell technologies and computational methods that have been developed for the single-cell omics analysis and how they have been applied to improve our understanding of the underlying mechanisms of biological and pathological phenomena at the single-cell level.

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