Leuprorelin Suppresses Angiogenesis and Malignant Progression in Endometrial Cancer via Downregulation of the ELAVL1/VEGFA Axis.
Leuprorelin may inhibit endometrial cancer progression by disrupting the ELAVL1/VEGFA axis, but further studies are needed to confirm these findings in humans.
Where it sits
this study against the rest of the leuprorelin corpusSummary and findings
Leuprorelin was evaluated for its effects on endometrial cancer (EC) cell lines and in a murine xenograft model. The study found that leuprorelin reduced proliferation, migration, and induced apoptosis in EC cells. Additionally, it suppressed HUVEC tube formation and tumor growth in vivo.
Abstract
Leuprorelin, a gonadotropin-releasing hormone (GnRH) agonist, is currently used clinically to suppress estrogen-dependent endometrial cancer (EC) through pituitary desensitization. However, whether this agent exerts direct anti-neoplastic effects via post-transcriptional regulatory mechanisms remains unclear. The phenotypic effects of leuprorelin were evaluated in EC cell lines using colony formation, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, Transwell migration, wound healing, flow cytometry, and HUVEC tube formation assays. Mechanistic exploration employed RNA immunoprecipitation (RIP), mRNA decay kinetics analysis, and RNA fluorescence in situ hybridization combined with immunofluorescence microscopy. A murine xenograft model system was implemented for in vivo validation studies. Leuprorelin treatment significantly reduced proliferation and migration of EC cells, induced apoptosis, and suppressed HUVEC tube formation. At the molecular level, leuprorelin administration reduced cytoplasmic accumulation of ELAVL1, an RNA-binding protein that physiologically associates with VEGFA transcripts and enhances their stability. This reduction resulted in accelerated decay of VEGFA mRNA and subsequent downregulation of VEGFA protein expression. Forced overexpression of VEGFA substantially abrogated the anti-tumor effects mediated by leuprorelin. In nude mouse xenograft models, leuprorelin administration suppressed tumor growth and tumor-associated neovascularization, effects that were reversed upon VEGFA overexpression. Leuprorelin impedes EC progression by disrupting ELAVL1-mediated stabilization of VEGFA mRNA, highlighting the ELAVL1/VEGFA axis as a potential therapeutic target for anti-angiogenic therapeutic intervention.
Background
Not reported in abstract.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
Not reported in abstract.
Limitations
Not reported in abstract.