MP29-07 LOSS OF MIR-21 DELAYS MYC-DRIVEN PROSTATE CANCER PROGRESSION IN THE HI-MYC TRANSGENIC MOUSE MODEL (2018)

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I1 Apr 2018MP29-07 LOSS OF MIR-21 DELAYS MYC-DRIVEN PROSTATE CANCER PROGRESSION IN THE HI-MYC TRANSGENIC MOUSE MODEL Kenji Zennami, Fatima Rafiqi, Ross Liao, Kim Sealover, Brian Simons, and Shawn Lupold Kenji ZennamiKenji Zennami More articles by this author , Fatima RafiqiFatima Rafiqi More articles by this author , Ross LiaoRoss Liao More articles by this author , Kim SealoverKim Sealover More articles by this author , Brian SimonsBrian Simons More articles by this author , and Shawn LupoldShawn Lupold More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.927AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES MicroRNA 21 (miR-21) is overexpressed in virtually all types of cancers including prostate cancer (PCa). We have previously reported that the androgen receptor (AR) induces miR-21 expression, and that elevated miR-21 is sufficient to drive PCa growth and castration resistance. However, the role of miR-21 in PCa initiation and progression has not been fully elucidated. To determine if the absence of miR-21 inhibits or delays prostate cancer incidence or progression, we crossed miR-21 KO mice with Hi-Myc mice. In this study, we identify that loss of miR-21 delays Myc-driven prostate cancer progression in the Hi-Myc transgenic mouse model. METHODS miR-21 KO mice were backcrossed to FVB mice to generation F10. Resulting miR-21 WT or KO FVB progeny were crossed with Hi-Myc mice to generate Hi-Myc/miR-21 WT or KO mice. Prostates were harvested at 4 weeks (n=10), 3 months (n=10), 5 months (n=58), 6 months (n=25), 8 months (n=20), 9 months (n=19) and 13 months (n=15) of age and prostate weight, histology and protein expression levels were quantified. Castration was performed at 8m and prostates were subsequently harvested at 9m or 13m to examine the effect of castration. RESULTS Hi-Myc/miR-21 KO mice demonstrated a marked reduction in adenocarcinoma when compared to Hi-Myc/miR-21 WT mice at 5m (Fig. 1A, 1B). This is apparent in the reduced weight of effected prostate lobes of Hi-Myc/miR-21 KO versus WT mice at 8m (Fig. 1C). Protein levels of established miR-21 target genes, PDCD4 and PTEN, were up-regulated in the prostates of Hi-Myc/miR-21 KO mice (Fig. 1D). However, miR-21 KO did not affect prostatic intraepithelial neoplasia (PIN) development (Fig. 2A) or cancer progression after castration (Fig. 2B, 2C). CONCLUSIONS Our results demonstrate that miR-21 contributes to Myc-driven prostate cancer progression and that endogenous miR-21 suppresses prostatic PDCD4 and PTEN protein expression levels. Therefore, targeting of miR-21 or its downstream target genes may be useful for cancer prevention or cancer therapy. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e368 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Kenji Zennami More articles by this author Fatima Rafiqi More articles by this author Ross Liao More articles by this author Kim Sealover More articles by this author Brian Simons More articles by this author Shawn Lupold More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...