Pd41-05 Mir-299-3p Inhibits Cell Proliferation, Migration, Invasion and Angiogenesis Through Vegfa in Upper Tract Urothelial Carcinoma

You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma III (PD41)1 May 2024PD41-05 MIR-299-3P INHIBITS CELL PROLIFERATION, MIGRATION, INVASION AND ANGIOGENESIS THROUGH VEGFA IN UPPER TRACT UROTHELIAL CARCINOMA Wei-Chi Hsu, Jhen-Hao Jhan, Chien-Sheng Wang, Yi-Chen Lee, Wei-Ming Li, Lin-Li Chang, A-Mei Huang, Hui-Hui Lin, Che-Wei Chang, Wen-Jeng Wu, Ching-Chia Li, and Hung-Lung Ke Wei-Chi HsuWei-Chi Hsu , Jhen-Hao JhanJhen-Hao Jhan , Chien-Sheng WangChien-Sheng Wang , Yi-Chen LeeYi-Chen Lee , Wei-Ming LiWei-Ming Li , Lin-Li ChangLin-Li Chang , A-Mei HuangA-Mei Huang , Hui-Hui LinHui-Hui Lin , Che-Wei ChangChe-Wei Chang , Wen-Jeng WuWen-Jeng Wu , Ching-Chia LiChing-Chia Li , and Hung-Lung KeHung-Lung Ke View All Author Informationhttps://doi.org/10.1097/01.JU.0001008568.76803.f1.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Upper tract urothelial carcinoma (UTUC) is a rare tumor with extraordinarily different feature between Eastern and Western countries. Vascular endothelial growth factor-A (VEGFA) was originally shown to be secreted signaling protein as well as a regulator of vascular development and cancer progression. MiR-299-3p governs tumor suppressive functions in several tumors. We aimed to elucidate the molecular mechanism underlying the regulation of VEGFA by miR-299-3p in UTUC. METHODS: VEGFA expression was evaluated by immunohistochemistry in one hundred and forty human UTUC tissues. We demonstrated that the regulatory relationship between VEGFA and miR-299-3p by real-time PCR, western blot, ELISA and dual luciferase reporter assay by two UTUC cell lines. The role of the miR-299-3p/VEGFA pathway in proliferation, motility, invasion and tube formation was analyzed in vitro. RESULTS: VEGFA high expression is significantly associated to stage (p=0.005), grade (p=0.004), distant metastasis (p=0.003), and cancer death (p=0.001). High VEGFA expression was correlated with poor progression-free survival(p=0.001) and cancer-specific survival (p<0.001). Knock-down the expression of VEGFA repressed UTUC cell proliferation, migration and invasion in vitro and miR-299-3p inhibited VEGFA protein expression by directly targeting its 3'-UTR. VEGFA overexpression reversed the effect of miR-299-3p in UTUC cells. In addition, UTUC cells mediated tube formation ability of Human Umbilical Vein Endothelial Cells (HUVECs) through miR-299-3p/VEGFA. The miR-299-3p/ VEGFA also suppress UTUC cell function by regulating the expression of P18, Cyclin E2 and Calponin-1. CONCLUSIONS: These findings suggest that miR-299-3p suppress UTUC cell proliferation, migration, invasion and angiogenesis by targeting VEGFA. Both VEGFA and miR-299-3p could be possible therapeutic targets in UTUC. Source of Funding: N/A © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e887 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Wei-Chi Hsu More articles by this author Jhen-Hao Jhan More articles by this author Chien-Sheng Wang More articles by this author Yi-Chen Lee More articles by this author Wei-Ming Li More articles by this author Lin-Li Chang More articles by this author A-Mei Huang More articles by this author Hui-Hui Lin More articles by this author Che-Wei Chang More articles by this author Wen-Jeng Wu More articles by this author Ching-Chia Li More articles by this author Hung-Lung Ke More articles by this author Expand All Advertisement PDF downloadLoading ...