Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea.
Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon 34113, Korea.
Mol Cells. 2023 May 31;46(5):298-308. doi: 10.14348/molcells.2023.2148. Epub 2023 Mar 10.
Gastric cancer (GC) is a complex disease influenced by multiple genetic and epigenetic factors. Chronic inflammation caused by 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 in GC using quantitative reverse transcription PCR with 174 paired samples of GC tumors and adjacent normal tissues. Transcriptional activation of 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 was hypomethylated in GC cell lines that showed upregulation of TNS4. We also found a significant negative correlation between 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.
胃癌（GC）是一种受多种遗传和表观遗传因素影响的复杂疾病。 感染和饮食风险因素引起的慢性炎症可导致胃黏膜中异常 DNA 甲基化的积累，从而促进 GC 的发展。Tensin 4（TNS4）是 Tensin 蛋白家族的成员之一，定位于黏着斑，连接细胞外基质和细胞骨架网络。我们使用定量逆转录 PCR 对 174 对 GC 肿瘤组织和相邻正常组织样本进行分析，发现 TNS4 在 GC 中上调。即使在肿瘤发展的早期阶段， 也发生转录激活。在表达高到中等水平 TNS4 的 GC 细胞系（即 SNU-601、KATO III 和 MKN74）中，TNS4 耗竭降低了细胞增殖和迁移，而在那些表达较低水平 TNS4 的细胞系（即 SNU-638、MKN1 和 MKN45）中，TNS4 的异位表达增加了集落形成和细胞迁移。在 TNS4 上调的 GC 细胞系中， 启动子区域呈低甲基化。我们还根据癌症基因组图谱（TCGA）数据发现，在 250 个 GC 肿瘤中， 表达与 CpG 甲基化之间存在显著负相关。本研究阐明了 TNS4 激活的表观遗传机制以及 TNS4 在 GC 发展和进展中的功能作用，并为未来的 GC 治疗提供了一种可能的方法。
