Delivery of BR2-SOX17 fusion protein can inhibit cell survival, proliferation, and invasion in gastric cancer cells through regulating Klotho gene expression
Delivery of BR2-SOX17 fusion protein can inhibit cell survival, proliferation, and invasion in gastric cancer cells through regulating Klotho gene expression
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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
DOI：
10.1002/cbin.11407
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发表时间：
2020
影响因子：
3.9
通讯作者：
Xie Biao
中科院分区：
文献类型：
--
作者：
Yang Lixia;Wu Yue;He Heli;Hu Fan;Li Mei;Mo Li;Xiao You;Wang Xiaoyan;Xie Biao
进展期胃癌的预后较差，了解其生物学特性和新的靶向治疗的后续发展仍然是一个迫切需要。本研究旨在探讨BR 2（一种17氨基酸肽）-SOX 17（人类性别决定区Y（SRY）相关高迁移率族（HMG）盒蛋白家族成员17）融合蛋白对胃癌细胞Klothogene表达的影响。使用双荧光素酶报告基因测定和染色质免疫沉淀（ChIP）测定来测试SOX 17对胃癌细胞中Klothogene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价BR 2 ‐ SOX 17的治疗作用。结果表明，SOX 17通过与Klothogene启动子结合，增强了Klothogene在胃腺癌细胞中的表达。BR 2 ‐ SOX 17融合蛋白能有效地将SOX 17导入胃癌细胞，抑制胃癌细胞的增殖、集落形成和侵袭，增加E‐cadherin蛋白的表达，降低vimentin蛋白的表达，并诱导细胞凋亡。我们的研究结果表明SOX 17可以与Klothogene的启动子结合，从而增强Klothogene在胃癌细胞中的表达。BR 2 ‐ SOX 17融合蛋白是胃癌靶向治疗的有效药物。
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 onKlothogene expression in gastric cancer cells. The regulatory effects of SOX17 onKlothogene 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 enhancedKlothogene expression in gastric adenocarcinoma cells through binding to the promoter ofKlothogene. 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 ofKlothogene to enhanceKlothogene expression in gastric cancer cells. The fused BR2‐SOX17 protein is an effective agent for targeting therapy of gastric cancer.