Effects of PELP1 on proliferation, metastasis and angiogenesis of epithelial ovarian cancer.

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.