Ding Jishuang, Gao Wei, Yang Haiying, Duan Lei, Sun Dong, Liu Luguang, Qu Xianlin, Yu Hang, Xu Botao, Zhao Siwei, Wang Longgang, Chai Jie
Department of Gastroenterological Surgery, Shanxian Central Hospital, Heze, Shandong, China; Department of Gastroenterological Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong Cancer Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Department of Science and Technology Report Center, Shandong Institute of Scientific and Technical Information, China.
Pathol Res Pract. 2024 Feb;254:155095. doi: 10.1016/j.prp.2024.155095. Epub 2024 Jan 4.
To explore the role of Kelch repeat and BTB (POZ) domain containing 2 (KBTBD2) in Gastric cancer(GC) via studying the level of KBTBD2 and its impact on GC cells and mice model.
Expression of KBTBD2 in GC was analyzed by analysis of TCGA data, Western blotting and Real-time quantitative polymerasechain reaction (RT-qPCR). The role of KBTBD2 on GC cells proliferation, viability, invasion, migration and apoptosis in vitro were assessed by using western blotting，RT-qPCR，CCK-8, EDU, Colony Formation Assay, Wound healing assay, Transwell, JC-1 mitochondrial membrane potential and flow cytometry assay, respectively. And levels of Bcl-2, BAX, PARP, E-cadherin, Vimentin, N-cadherin, EGFR, SOS1, NROS, BRAF,ERK1/2 and GAPDH were tested by western blotting. Relation of KBTBD2 and epidermal growth factor receptor (EGFR) was predicted by KEGG analysis. KBTBD2 gene GSEA enrichment was analyzed by using R language. Moreover, CCK-8, western blotting, and wound healing assays were used to verify the correlation of KBTBD2 and EGFR pathway. Finally, tumor growth in mice was also investigated. Cells proliferation, migration and apoptosis were detected by Ki67 staining, Tunnel staining and mouse lung metastasis model.
KBTBD2 was highly expressed in GC, and was related to poor prognosis. Moreover, silencing KBTBD2 suppressed GC cell proliferation, migration and invasion, while also inhibited the EMT, but promoted apoptosis. At the same time, KBTBD2 overexpression showed opposite results. In addition, KBTBD2 regulated the EGFR pathway. Further, silencing KBTBD2 inhibited tumor growth, cell proliferation and migration but promoted apoptosis in vivo, and KBTBD2 overexpression showed opposite results.
KBTBD2 was highly expressed in GC. KBTBD2 promotes the progress of GC by activating EGFR signal pathway. KBTBD2 may thus be a novel target for treating GC.
通过研究含 Kelch 重复序列和 BTB（POZ）结构域 2（KBTBD2）的水平及其对胃癌（GC）细胞和小鼠模型的影响，探讨其在胃癌中的作用。
通过分析 TCGA 数据、蛋白质免疫印迹法和实时定量聚合酶链反应（RT-qPCR）分析 KBTBD2 在 GC 中的表达。分别使用蛋白质免疫印迹法、RT-qPCR、CCK-8、EDU、集落形成实验、划痕实验、Transwell、JC-1 线粒体膜电位和流式细胞术实验评估 KBTBD2 对 GC 细胞体外增殖、活力、侵袭、迁移和凋亡的作用。并通过蛋白质免疫印迹法检测 Bcl-2、BAX、PARP、E-钙黏蛋白、波形蛋白、N-钙黏蛋白、表皮生长因子受体（EGFR）、SOS1、NROS、BRAF、ERK1/2 和甘油醛-3-磷酸脱氢酶（GAPDH）的水平。通过 KEGG 分析预测 KBTBD2 与表皮生长因子受体（EGFR）的关系。使用 R 语言分析 KBTBD2 基因的基因集富集分析（GSEA）。此外，使用 CCK-8、蛋白质免疫印迹法和划痕实验验证 KBTBD2 与 EGFR 通路的相关性。最后，还研究了小鼠体内的肿瘤生长情况。通过 Ki67 染色、TUNEL 染色和小鼠肺转移模型检测细胞增殖、迁移和凋亡情况。
KBTBD2 在 GC 中高表达，且与预后不良相关。此外，沉默 KBTBD2 可抑制 GC 细胞增殖、迁移和侵袭，同时抑制上皮-间质转化（EMT），但促进凋亡。同时，KBTBD2 过表达则显示相反的结果。此外，KBTBD2 调节 EGFR 通路。进一步研究发现，沉默 KBTBD2 可抑制体内肿瘤生长、细胞增殖和迁移，但促进凋亡，而 KBTBD2 过表达则显示相反的结果。
KBTBD2 在 GC 中高表达。KBTBD2 通过激活 EGFR 信号通路促进 GC 的进展。因此，KBTBD2 可能是治疗 GC 的新靶点。
