Leuprorelin Suppresses Angiogenesis and Malignant Progression in Endometrial Cancer via Downregulation of the ELAVL1/VEGFA Axis.
- 1Department of Gynaecology, Shijiazhuang People's Hospital, Shijiazhuang City, Hebei Province, China.
- 2Department of Rehabilitation, Shijiazhuang People's Hospital, Shijiazhuang City, Hebei Province, China.
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.
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BibTeX
@article{zhang2026leuprorelin,
title = {{Leuprorelin Suppresses Angiogenesis and Malignant Progression in Endometrial Cancer via Downregulation of the ELAVL1/VEGFA Axis.}},
author = {NingNing Zhang and Fang Zhao and LiMei Tan},
journal = {Journal of biochemical and molecular toxicology},
year = {2026},
month = nov,
doi = {10.1002/jbt.71163},
url = {https://europepmc.org/article/MED/42967590},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Leuprorelin Suppresses Angiogenesis and Malignant Progression in Endometrial Cancer via Downregulation of the ELAVL1/VEGFA Axis.
AU - NingNing Zhang
AU - Fang Zhao
AU - LiMei Tan
PY - 2026
DA - 2026/11/01
JO - Journal of biochemical and molecular toxicology
DO - 10.1002/jbt.71163
UR - https://europepmc.org/article/MED/42967590
AB - 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.
SN - 1095-6670
SN - 1099-0461
ER -