文章：

PHF10抑制胃黏膜上皮分化并促进胃癌发生

PHF10 inhibits gastric epithelium differentiation and induces gastric cancer carcinogenesis 

原文发布日期：2024-08-10

英文摘要：

Gastric cancer (GC) is characterized with differentiation disorders, the precise mechanisms of which remain unknown. Our previous study showed that PHF10 exhibits oncogenic properties in GC, with its histological presentation indicating a potential role in the modulation of differentiation disorders in GC. This study reveals a significant upregulation of PHF10 in GC tissues, showing a negative correlation with differentiation level. PHF10 was found to impede the differentiation of GC cells while promoting their stemness properties. This was attributed to the formation of a positive feedback loop between PHF10 and E2F1, resulting in dysregulated expression levels in GC. Additionally, PHF10 was found to mediate the transcriptional repression of the target gene DUSP5 in GC cells through the assembly of the SWI/SNF complex, leading to an elevation in pERK1/2 levels. In GC tissues, a negative association was noted between the expression of E2F1 or PHF10 and DUSP5, whereas a positive correlation was observed between the expression of E2F1 or PHF10 and pERK1/2. Additional rescue experiments confirmed that the inhibitory effect on differentiation of GC cells by PHF10 is dependent on the DUSP5-pERK1/2 axis. The signaling cascade involving E2F1-PHF10-DUSP5-pERK1/2 was identified as an important player in regulating differentiation and stemness in GC cells. PHF10 emerges as a promising target for differentiation induction therapy in GC. 

摘要翻译：

胃癌（GC）的特征是分化异常，但其确切机制尚不明确。我们前期研究发现PHF10在GC中呈现致癌特性，其组织学表现提示该基因可能参与调控GC的分化障碍。本研究揭示PHF10在GC组织中显著上调，且与分化程度呈负相关。PHF10可阻碍GC细胞分化同时促进其干性特征，这归因于PHF10与E2F1之间形成的正反馈循环导致其在GC中的表达水平失调。此外，研究发现PHF10通过组装SWI/SNF复合物介导对靶基因DUSP5的转录抑制，进而升高pERK1/2水平。在GC组织中，E2F1或PHF10的表达与DUSP5呈负相关，而与pERK1/2呈正相关。补充挽救实验证实，PHF10对GC细胞分化的抑制作用依赖于DUSP5-pERK1/2轴。E2F1-PHF10-DUSP5-pERK1/2信号级联被确定为调控GC细胞分化和干性的重要通路。PHF10有望成为GC分化诱导治疗的潜在靶点。

原文链接：

PHF10 inhibits gastric epithelium differentiation and induces gastric cancer carcinogenesis