Gastric adenocarcinoma (GAC) is the third leading cause of cancer-related death worldwide. A high mortality rate and resistance to treatment protocols due to a heterogeneous molecular pathogenesis has made discovering the key etiologic molecular alterations of the utmost importance. The remarkable role played by epigenetic modifications in repressing or activating many cancer-related genes and forming new epigenetic signatures can affect cancer initiation and progression. Hence, targeting the key epigenetic drivers could potentially attenuate cancer progression. MLLs, ARID1A and EZH2 are among the major epigenetic players that are frequently mutated in GACs. In this paper, we have proposed the existence of a network between these proteins that, together with PCAF and KDM6A, control the 3D chromatin structure and regulate the expression of tumor suppressor genes (TSGs) and oncogenes in GAC. Therefore, we suggest that manipulating the expression of EZH2, PCAF, and KDM6A or their downstream targets may reduce the cancerous phenotype in GAC.

胃癌（GAC）是全球癌症相关死亡的第三大原因。由于异质分子发病机制导致的高死亡率和对治疗方案的抵抗使得发现最重要的关键病因分子改变。表观遗传修饰在抑制或激活许多癌症相关基因和形成新的表观遗传特征方面所起的显着作用可以影响癌症的发生和进展。因此，针对关键的表观遗传驱动因素可能会减缓癌症进展。MLL、ARID1A 和 EZH2 是在 GAC 中经常发生突变的主要表观遗传参与者。在本文中，我们提出在这些蛋白质之间存在一个网络，与 PCAF 和 KDM6A 一起，控制 3D 染色质结构并调节 GAC 中肿瘤抑制基因 (TSG) 和癌基因的表达。因此，我们建议操纵EZH2、PCAF和KDM6A或其下游靶标可能会降低 GAC 中的癌性表型。