Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.
Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.
Oncol Rep. 2021 Apr;45(4). doi: 10.3892/or.2021.7993. Epub 2021 Mar 2.
Pathological changes in the epigenetic landscape of chromatin are hallmarks of cancer. Our previous study showed that global methylation of promoters may increase or decrease during the transition from gastric mucosa to intestinal metaplasia (IM) to gastric cancer (GC). Here, CpG hypomethylation of the serine/threonine kinase promoter in IM and GC was detected in a reduced representation bisulfite sequencing database. hypomethylation, which resulted in its upregulation in 120 cases of primary GC, was confirmed. Using public genome‑wide histone modification data, upregulation of promoter activity was detected in primary GC but not in normal mucosae, suggesting that may be repressed in gastric mucosa but activated in GC as a consequence of hypomethylation‑associated chromatin remodeling. knockdown suppressed the proliferation, colony formation and migration activities of GC cells , whereas stable overexpression of STK31 promoted the proliferation, colony formation, and migration activities of GC cells and tumorigenesis in nude mice. Patients with GC in which was upregulated exhibited significantly shorter survival times in a combined cohort. Thus, activation of by chromatin remodeling may be associated with gastric carcinogenesis and also may help predict GC prognosis.
染色质表观遗传景观中的病理变化是癌症的标志。我们之前的研究表明，在从胃黏膜到肠上皮化生（IM）再到胃癌（GC）的转变过程中，启动子的整体甲基化可能增加或减少。在这里，在减少代表性亚硫酸氢盐测序数据库中检测到 IM 和 GC 中丝氨酸/苏氨酸激酶启动子的 CpG 低甲基化。在 120 例原发性 GC 中，其结果导致其上调，得到了证实。使用公共全基因组组蛋白修饰数据，在原发性 GC 中检测到 启动子活性的上调，但在正常黏膜中未检测到，这表明 在胃黏膜中可能受到抑制，但由于与低甲基化相关的染色质重塑，在 GC 中被激活。 STK31 的下调抑制了 GC 细胞的增殖、集落形成和迁移活性，而 STK31 的稳定过表达则促进了 GC 细胞的增殖、集落形成、迁移活性和裸鼠肿瘤的发生。在联合队列中，上调的 GC 患者的存活时间明显缩短。因此，染色质重塑激活可能与胃癌的发生有关，也可能有助于预测 GC 的预后。
