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• W2604431015 abstract "You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology IV1 Apr 2017MP99-16 MIR-221 MODULATES TUMOR GROWTH IN VIVO AND IS A REGULATOR OF TGF-? SIGNALING IN HUMAN PROSTATE CANCER Eugenio Zoni, Markus Krebs, Philip Herreiner, Charis Kalogiro, Lanpeng Chen, Ewa Snaar-Jagalska, George N. Thalmann, Marianna Kruithof-de Julio, Hubertus Riedmiller, Burkhard Kneitz, and Martin Spahn Eugenio ZoniEugenio Zoni More articles by this author , Markus KrebsMarkus Krebs More articles by this author , Philip HerreinerPhilip Herreiner More articles by this author , Charis KalogiroCharis Kalogiro More articles by this author , Lanpeng ChenLanpeng Chen More articles by this author , Ewa Snaar-JagalskaEwa Snaar-Jagalska More articles by this author , George N. ThalmannGeorge N. Thalmann More articles by this author , Marianna Kruithof-de JulioMarianna Kruithof-de Julio More articles by this author , Hubertus RiedmillerHubertus Riedmiller More articles by this author , Burkhard KneitzBurkhard Kneitz More articles by this author , and Martin SpahnMartin Spahn More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.3102AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate Cancer (PCa) is the most common cancer diagnosed in males and the second leading cause of death from cancer in men. Despite the advances in cancer therapy, when PCa progress to castration resistant phase, patients develop incurable bone metastases. Therefore, understanding of the processes that regulate homing and survival of metastatic cancer cells in the bone is crucial for the identification of new therapies. TGF-β signaling plays a major role in bone remodeling and according to the ″vicious cycle hypothesis″ is a master regulator of maintenance of prostate cancer cells in lytic bone lesions. microRNAs (miRs) are a class of small non-coding RNAs that regulates many biological process. miR-221 expression has been previously associated with prostate cancer progression. Here we studied the effect of miR-221 on TGF-β signaling and the impact of miR-221 on tumor growth in vivo. METHODS miR-221 was overexpressed in PC3 and RWPE-1 cells and PMEPA was monitored by RT-qPCR and western blot. Expression of miR-221 in PC3 and RWPE-1 cells was assessed by RT-qPCR. Predicted targets were identified in silico (Targetscan and microRNA.org). Luciferase assay was used to investigate the interaction between miR-221 and PMEPA1. For zebrafish experiment, fluorescently labelled PC-3M-Pro4 cells overexpressing miR-221 were injected in the duct of cuvier of zebrafish embryos. RESULTS We found that miR-221 overexpression resulted in decreased PMEPA1 mRNA and protein in PC-3 human prostate cancer cells. PMEPA1 is a master regulator of TGF-β signaling and luciferase reporter assay revealed that miR-221 can directly interact with PMEPA1 3′ UTR. Our experiments showed an enhancement of the proliferative effect of TGF-β in PC-3 cells, following enforced miR-221 expression. In conclusion, we observed increased Smad2 activation upon TGF-β treatment in miR-221 overexpressing PC-3 cells. Inoculation of fluorescently labelled highly metastatic PC-3M-Pro4 cells overexpressing miR-221 in the Duct of Cuvier (DC) of zebrafish embryos resulted reduced tumor burden compared to control. Finally, we found an inverse correlation between miR-221 and PMEPA1 expression in normal vs. tumor tissue collected from PCa patients. CONCLUSIONS Our results indicate that miR-221 is a regulator of TGF-β signaling via modulation of PMEPA1 and miR-221 overexpression can reduce tumor growth in vivo. Therefore, miR-221 represents an interesting molecule to target PCa and to interfere with the maintenance of PCa cells in the bone microenvironment. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1326 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Eugenio Zoni More articles by this author Markus Krebs More articles by this author Philip Herreiner More articles by this author Charis Kalogiro More articles by this author Lanpeng Chen More articles by this author Ewa Snaar-Jagalska More articles by this author George N. Thalmann More articles by this author Marianna Kruithof-de Julio More articles by this author Hubertus Riedmiller More articles by this author Burkhard Kneitz More articles by this author Martin Spahn More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ..." @default.
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• W2604431015 title "MP99-16 MIR-221 MODULATES TUMOR GROWTH IN VIVO AND IS A REGULATOR OF TGF-? SIGNALING IN HUMAN PROSTATE CANCER" @default.
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