Department of Obstetrics, Fokind Hospital Affiliated to Tibet University, Lhasa, Tibet, China.
Department of Intensive Care Unit, Huai'an Second People's Hospital and The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu, China.
Environ Toxicol. 2023 Mar;38(3):685-693. doi: 10.1002/tox.23720. Epub 2022 Dec 1.
Human discs large-associated protein 5 (DLGAP5), a microtubule-associated protein, has been reported to be upregulated in several tumors. However, the role of DLGAP5 in endometrial cancer (EC) progression and the related underlying mechanism were still unknown. A bioinformatics analysis was performed to analyze the expression and prognostic significance of DLGAP5 in EC tissues using TCGA, CPTAC, Human Protein Atlas, and GSE63678 databases, UALCAN web tool, and the Kaplan-Meier plotter. Effects of DLGAP on EC cell malignant properties were evaluated by CCK-8, flow cytometry analysis, TUNEL assay, caspase-3 activity assay, and Transwell invasion assay. The expression of DLGAP5, Wnt3, c-Myc, Ki67, and cleaved caspase-3 was detected by western blot analysis. DLGAP5 was highly expressed and correlated with poor prognosis in EC patients. DLGAP5 knockdown inhibited proliferation and invasion, triggered apoptosis, and increased caspase-3 activity in EC cells. Additionally, DLGAP5 knockdown inactivated the Wnt/β-catenin signaling pathway in EC cells. Moreover, β-catenin overexpression abolished the effects of DLGAP5 knockdown on the malignant phenotypes of EC cells. DLGAP5 silencing suppressed the malignant properties in EC cells by inactivating the Wnt/β-catenin pathway.
人类椎间盘大相关蛋白 5（DLGAP5）是一种微管相关蛋白，已被报道在多种肿瘤中上调。然而，DLGAP5 在子宫内膜癌（EC）进展中的作用及其相关的潜在机制尚不清楚。通过 TCGA、CPTAC、Human Protein Atlas 和 GSE63678 数据库、UALCAN 网络工具和 Kaplan-Meier 绘图仪进行了生物信息学分析，以分析 DLGAP5 在 EC 组织中的表达和预后意义。通过 CCK-8、流式细胞术分析、TUNEL 测定、caspase-3 活性测定和 Transwell 侵袭测定评估了 DLGAP 对 EC 细胞恶性特性的影响。通过 Western blot 分析检测了 DLGAP5、Wnt3、c-Myc、Ki67 和 cleaved caspase-3 的表达。在 EC 患者中，DLGAP5 表达上调，与预后不良相关。DLGAP5 敲低抑制了 EC 细胞的增殖和侵袭，触发了凋亡，并增加了 EC 细胞中的 caspase-3 活性。此外，在 EC 细胞中敲低 DLGAP5 可使 Wnt/β-catenin 信号通路失活。此外，β-catenin 过表达消除了 DLGAP5 敲低对 EC 细胞恶性表型的影响。DLGAP5 沉默通过使 Wnt/β-catenin 通路失活来抑制 EC 细胞的恶性特性。
