General Surgery Department of Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, Shanxi, China.
Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China.
Neoplasma. 2023 Dec;70(6):733-746. doi: 10.4149/neo_2023_230104N8. Epub 2023 Nov 28.
F-box and WD repeat domain containing 7 (FBXW7) is an aboriginal and high-frequency mutant gene associated with esophageal squamous cell carcinoma (ESCC). This study was designed to determine the clinical value and molecular mechanisms of FBXW7 in the development of ESCC. The clinical significance of FBXW7 was analyzed in ESCC from TCGA data. The effects of FBXW7 on proliferation, colony formation, migration and invasion, angiogenesis, and apoptosis were tested in ESCC cells. PCR-array, sphere formation assay, and quantitative real-time polymerase chain reaction (qPCR) were used to explore the mechanism of FBXW7. FBXW7 was a significantly mutated gene in ESCC. It was an independent and potential predictor for survival in ESCC patients. In addition, FBXW7 overexpression significantly inhibited ESCC cell proliferation, migration, invasion, angiogenesis, and promoted cell apoptosis. PCR array revealed that FBXW7 overexpression leads to a significant change of gene expressions associated with angiogenesis, cell senescence, and DNA damage and repair. Sphere formation assay and qPCR showed FBXW7 was associated with ESCC stem cell formation. Our results suggest that FBXW7 may act as a tumor suppressor by repressing cancer stem cell formation and regulating tumor angiogenesis, cell senescence, DNA damage, and repair in ESCC.
F-box 和 WD 重复结构域包含 7（FBXW7）是一种与食管鳞癌（ESCC）相关的原始高频突变基因。本研究旨在确定 FBXW7 在 ESCC 发展中的临床价值和分子机制。从 TCGA 数据中分析了 FBXW7 在 ESCC 中的临床意义。在 ESCC 细胞中检测了 FBXW7 对增殖、集落形成、迁移和侵袭、血管生成和细胞凋亡的影响。PCR 数组、球体形成测定和定量实时聚合酶链反应（qPCR）用于探索 FBXW7 的机制。FBXW7 是 ESCC 中的一个显著突变基因。它是 ESCC 患者生存的独立和潜在预测因子。此外，FBXW7 过表达显著抑制 ESCC 细胞增殖、迁移、侵袭、血管生成，并促进细胞凋亡。PCR 数组显示 FBXW7 过表达导致与血管生成、细胞衰老和 DNA 损伤和修复相关的基因表达发生显著变化。球体形成测定和 qPCR 显示 FBXW7 与 ESCC 干细胞形成有关。我们的结果表明，FBXW7 可能通过抑制癌症干细胞形成和调节 ESCC 中的肿瘤血管生成、细胞衰老、DNA 损伤和修复来发挥肿瘤抑制因子的作用。
