Xie Lele, Sun Congcong, Mao Yanhua, Huang Xiyue, Yang Xiao, Huang Jinglin, Zhang Yingfeng, Li Changjiang, Yang Weifeng, Zhang Wenwen, Wang Jia
Department of Obstetrics and Gynecology, The University-Town Hospital of Chongqing Medical University, No. 55, Daxuecheng Middle Road, Chongqing, 401331, China.
Department of Obstetrics, Maternal and child health care hospital of Ningxia Hui Autonomous Region, Ningxia, China.
Med Oncol. 2025 Jul 26;42(9):379. doi: 10.1007/s12032-025-02908-w.
To investigate the effects of Proline-, Glutamic acid- and Leucine-rich protein 1(PELP1) on the biological behaviors of epithelial ovarian cancer (EOC) cells and its role in promoting angiogenesis through the regulation of VEGFA expression and secretion. Bioinformatics analysis was performed to evaluate the correlation between PELP1 and VEGFA. The expression levels and subcellular localization of PELP1 and VEGFA in EOC cell lines were assessed using Western blot (WB), quantitative real-time PCR (qRT-PCR) and immunofluorescence. Functional assays, including EdU proliferation assays, wound healing assays, Transwell invasion assays and WB were conducted to examine the effects of PELP1 overexpression. Conditioned medium (CM) from PELP1-overexpression cells was used to culture human umbilical vein endothelial cells (HUVECs) and angiogenesis was evaluated using Transwell migration, wound healing, and tube formation assays. VEGFA expression and secretion were analyzed by immunofluorescence, qRT-PCR, and enzyme-linked immunosorbent assays (ELISA). WB and ELISA were performed to validate the effects of the VEGFA inhibitor (HY-117661) on both the expression and secretion of VEGFA. Functional rescue experiments, including migration and tube formation assays, were conducted to verify whether PELP1 regulated angiogenesis through VEGFA. Bioinformatics analysis revealed a positive correlation between PELP1 and VEGFA. Both proteins were significantly upregulated in EOC cells compared to normal ovarian epithelial cells. Overexpression of PELP1 enhanced proliferation, migration, invasion and the expression of metastasis-associated proteins, including N-cadherin and Vimentin. Additionally, PELP1 upregulated VEGFA expression and secretion, which subsequently promoted HUVEC migration and angiogenesis. PELP1 promotes EOC progression by enhancing cellular proliferation, metastasis and angiogenesis through the regulation of VEGFA. These findings suggest that PELP1 could serve as a potential therapeutic target for EOC.
探讨富含脯氨酸、谷氨酸和亮氨酸蛋白1（PELP1）对上皮性卵巢癌（EOC）细胞生物学行为的影响及其通过调控VEGFA表达和分泌促进血管生成的作用。进行生物信息学分析以评估PELP1与VEGFA之间的相关性。使用蛋白质印迹法（WB）、定量实时聚合酶链反应（qRT-PCR）和免疫荧光法评估EOC细胞系中PELP1和VEGFA的表达水平及亚细胞定位。进行包括EdU增殖试验、伤口愈合试验、Transwell侵袭试验和WB在内的功能试验，以检测PELP1过表达的影响。用PELP1过表达细胞的条件培养基（CM）培养人脐静脉内皮细胞（HUVECs），并使用Transwell迁移、伤口愈合和管腔形成试验评估血管生成。通过免疫荧光、qRT-PCR和酶联免疫吸附测定（ELISA）分析VEGFA的表达和分泌。进行WB和ELISA以验证VEGFA抑制剂（HY-117661）对VEGFA表达和分泌的影响。进行包括迁移和管腔形成试验在内的功能挽救实验，以验证PELP1是否通过VEGFA调节血管生成。生物信息学分析显示PELP1与VEGFA之间呈正相关。与正常卵巢上皮细胞相比，这两种蛋白在EOC细胞中均显著上调。PELP1过表达增强了增殖、迁移、侵袭以及包括N-钙黏蛋白和波形蛋白在内的转移相关蛋白的表达。此外，PELP1上调VEGFA的表达和分泌，随后促进HUVEC迁移和血管生成。PELP1通过调控VEGFA增强细胞增殖、转移和血管生成，从而促进EOC进展。这些发现表明PELP1可能成为EOC的潜在治疗靶点。
