Gastric cancer, is the fourth most common tumour type yet, ranks second in terms of the prevalence of cancer‐related deaths worldwide. CXXC finger protein 4 (CXXC4) has been considered as a novel cancer suppressive factor, including gastric cancer. This study attempted to investigate the possible function of CXXC4 in gastric cancer and the underlying mechanism. The binding of the ETS domain‐containing protein‐1 (ELK1) to the long non‐coding RNA MIR100HG promoter region was identified. Then, their expression patterns in gastric cancer tissues and cells (SGC7901) were detected. A CCK‐8 assay was used to detect SGC7901 cell proliferation. Subsequently, SGC7901 cells were co‐cultured with CD3+ T cells, followed by measurement of CD3+ T cell proliferation, magnitude of IFN‐γ+ T cell population and IFN‐γ secretion. A nude mouse model was subsequently developed for in vivo validation of the in vitro results. Low CXXC4 expression was found in SGC7901 cells. Nuclear entry of ELK1 can be inhibited by suppression of the extent of ELK1 phosphorylation. Furthermore, ELK1 is able to bind the MIR100HG promoter. Overexpression of CXXC4 resulted in weakened binding of ELK1 to the MIR100HG promoter, leading to a reduced proliferative potential of SGC7901 cells, and an increase in IFN‐γ secretion from CD3+ T cells. Moreover, in vivo experiments revealed that CXXC4 inhibited immune escape of gastric cancer cells through the ERK1/2 axis. Inhibition of the CXXC4/ELK1/MIR100HG pathway suppressed the immune escape of gastric cancer cells, highlighting a possible therapeutic target for the treatment of gastric cancer.

中文翻译：

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CXXC手指蛋白4抑制CDK18-ERK1 / 2轴，从而通过ELK1 / MIR100HG途径抑制胃癌细胞的免疫逃逸。

胃癌是目前第四大最常见的肿瘤类型，在全世界因癌症而死亡的患病率中排名第二。CXXC手指蛋白4（CXXC4）被认为是一种新型的癌症抑制因子，包括胃癌。本研究试图探讨CXXC4在胃癌中的可能功能及其潜在机制。鉴定出含有ETS结构域的蛋白-1（ELK1）与长的非编码RNA MIR100HG启动子区域的结合。然后，检测它们在胃癌组织和细胞（SGC7901）中的表达模式。使用CCK-8测定法检测SGC7901细胞增殖。随后，将SGC7901细胞与CD3 + T细胞共培养，然后测量CD3 + T细胞增殖，IFN-γ+ T细胞数量和IFN-γ分泌。随后开发了裸鼠模型以用于体外验证体外结果。在SGC7901细胞中发现低CXXC4表达。ELK1的核进入可以通过抑制ELK1磷酸化的程度来抑制。此外，ELK1能够结合MIR100HG启动子。CXXC4的过度表达导致ELK1与MIR100HG启动子的结合减弱，从而导致SGC7901细胞的增殖潜能降低，并且CD3 + T细胞的IFN-γ分泌增加。此外，体内实验表明CXXC4通过ERK1 / 2轴抑制胃癌细胞的免疫逃逸。CXXC4 / ELK1 / MIR100HG途径的抑制抑制了胃癌细胞的免疫逃逸，突出了治疗胃癌的可能治疗靶标。在SGC7901细胞中发现低CXXC4表达。ELK1的核进入可以通过抑制ELK1磷酸化的程度来抑制。此外，ELK1能够结合MIR100HG启动子。CXXC4的过表达导致ELK1与MIR100HG启动子的结合减弱，从而导致SGC7901细胞的增殖潜能降低，并且CD3 + T细胞的IFN-γ分泌增加。此外，体内实验表明CXXC4通过ERK1 / 2轴抑制胃癌细胞的免疫逃逸。CXXC4 / ELK1 / MIR100HG途径的抑制抑制了胃癌细胞的免疫逃逸，突出了治疗胃癌的可能治疗靶标。在SGC7901细胞中发现低CXXC4表达。ELK1的核进入可以通过抑制ELK1磷酸化的程度来抑制。此外，ELK1能够结合MIR100HG启动子。CXXC4的过度表达导致ELK1与MIR100HG启动子的结合减弱，从而导致SGC7901细胞的增殖潜能降低，并且CD3 + T细胞的IFN-γ分泌增加。此外，体内实验表明CXXC4通过ERK1 / 2轴抑制胃癌细胞的免疫逃逸。CXXC4 / ELK1 / MIR100HG途径的抑制抑制了胃癌细胞的免疫逃逸，突出了治疗胃癌的可能治疗靶标。ELK1能够结合MIR100HG启动子。CXXC4的过度表达导致ELK1与MIR100HG启动子的结合减弱，从而导致SGC7901细胞的增殖潜能降低，并且CD3 + T细胞的IFN-γ分泌增加。此外，体内实验表明CXXC4通过ERK1 / 2轴抑制胃癌细胞的免疫逃逸。CXXC4 / ELK1 / MIR100HG途径的抑制抑制了胃癌细胞的免疫逃逸，突出了治疗胃癌的可能治疗靶标。ELK1能够结合MIR100HG启动子。CXXC4的过度表达导致ELK1与MIR100HG启动子的结合减弱，从而导致SGC7901细胞的增殖潜能降低，并且CD3 + T细胞的IFN-γ分泌增加。此外，体内实验表明CXXC4通过ERK1 / 2轴抑制胃癌细胞的免疫逃逸。CXXC4 / ELK1 / MIR100HG途径的抑制抑制了胃癌细胞的免疫逃逸，突出了治疗胃癌的可能治疗靶标。体内实验表明，CXXC4通过ERK1 / 2轴抑制胃癌细胞的免疫逃逸。CXXC4 / ELK1 / MIR100HG途径的抑制抑制了胃癌细胞的免疫逃逸，突出了治疗胃癌的可能治疗靶标。体内实验表明，CXXC4通过ERK1 / 2轴抑制胃癌细胞的免疫逃逸。CXXC4 / ELK1 / MIR100HG途径的抑制抑制了胃癌细胞的免疫逃逸，突出了治疗胃癌的可能治疗靶标。