Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Epigenetic Activation of Tensin 4 Promotes Gastric Cancer Progression

  • Haejeong Heo (Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Hee-Jin Kim (Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Keeok Haam (Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Hyun Ahm Sohn (Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Yang-Ji Shin (Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Hanyong Go (Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Hyo-Jung Jung (Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Jong-Hwan Kim (Korea Bioinformation Center, KRIBB) ;
  • Sang-Il Lee (Department of Surgery, College of Medicine, Chungnam National University) ;
  • Kyu-Sang Song (Department of Pathology, College of Medicine, Chungnam National University) ;
  • Min-Ju Kim (Department of Pharmacy, College of Pharmacy, Pusan National University) ;
  • Haeseung Lee (Department of Pharmacy, College of Pharmacy, Pusan National University) ;
  • Eun-Soo Kwon (Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Seon-Young Kim (Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology (UST)) ;
  • Yong Sung Kim (Functional Genomics Institute, PDXen Biosystems Co.) ;
  • Mirang Kim (Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
  • Received : 2022.09.19
  • Accepted : 2022.12.18
  • Published : 2023.05.31
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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

Acknowledgement

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (2019R1A2C1087104), the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (HI21C0538), National Research Council of Science & Technology (NST) Aging Convergence Research Center (CRC22011-400), and the Korea Research Institute of Bioscience & Biotechnology (KRIBB) Research Initiative Program (KGM5192221).

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