The prognosis of advanced gastric cancer is poor and understanding the biology and subsequent development of new targeting therapy is still an urgent need. This study was conducted to explore the effect of BR2 (a 17‐amino acid peptide)‐SOX17 (human sex determining region Y (SRY)‐related high‐mobility group (HMG) box protein family member 17) fusion protein on Klotho gene expression in gastric cancer cells. The regulatory effects of SOX17 on Klotho gene in gastric cancer cells were tested using dual‐luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay. The therapeutic effects of BR2‐SOX17 were evaluated by proliferation, colony formation, invasion assay, and cell apoptosis analysis. Results showed that SOX17 enhanced Klotho gene expression in gastric adenocarcinoma cells through binding to the promoter of Klotho gene. BR2‐SOX17 fusion protein was effective in delivering SOX17 into gastric cancer cells and subsequently inhibited the cell proliferation, colony formation, and invasion, increased E‐cadherin protein expression, decreased vimentin protein expression, as well as induced apoptosis. Our findings suggested SOX17 can bind to the promoter of Klotho gene to enhance Klotho gene expression in gastric cancer cells. The fused BR2‐SOX17 protein is an effective agent for targeting therapy of gastric cancer.

中文翻译：

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BR2-SOX17融合蛋白的递送可通过调节Klotho基因表达抑制胃癌细胞的存活、增殖和侵袭。

晚期胃癌的预后较差，了解生物学和后续开发新的靶向治疗仍是迫切需要。本研究旨在探讨 BR2（一种 17 个氨基酸的肽）-SOX17（人类性别决定区 Y (SRY) 相关高迁移率组 (HMG) 盒蛋白家族成员 17）融合蛋白对Klotho基因表达的影响在胃癌细胞中。使用双荧光素酶报告基因检测和染色质免疫沉淀 (ChIP) 检测检测SOX17 对胃癌细胞Klotho基因的调节作用。通过增殖、集落形成、侵袭试验和细胞凋亡分析来评估 BR2-SOX17 的治疗效果。结果表明 SOX17 增强了Klotho通过与Klotho基因的启动子结合在胃腺癌细胞中的基因表达。BR2-SOX17 融合蛋白可有效地将 SOX17 递送到胃癌细胞中，随后抑制细胞增殖、集落形成和侵袭，增加 E-cadherin 蛋白表达，降低波形蛋白表达，并诱导细胞凋亡。我们的研究结果表明，SOX17 可以与Klotho基因的启动子结合，从而增强胃癌细胞中Klotho基因的表达。融合的 BR2-SOX17 蛋白是一种有效的胃癌靶向治疗药物。