MP33-15 MAPPING GENETIC VARIABILITY IN MATURE MIRNAS AND MIRNA BINDING SITES IN PROSTATE CANCER (2021)

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I (MP33)1 Sep 2021MP33-15 MAPPING GENETIC VARIABILITY IN MATURE MIRNAS AND MIRNA BINDING SITES IN PROSTATE CANCER Bongyong Lee, Jian-Liang Li, John Marchica, Mark Mercola, Vipul Patel, and Ranjan Perera Bongyong LeeBongyong Lee More articles by this author , Jian-Liang LiJian-Liang Li More articles by this author , John MarchicaJohn Marchica More articles by this author , Mark MercolaMark Mercola More articles by this author , Vipul PatelVipul Patel More articles by this author , and Ranjan PereraRanjan Perera More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002042.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: MicroRNAs (miRNAs) regulate diverse cancer hallmarks through sequence-specific regulation of gene expression, so genetic variability in their seed sequences or target sites could be responsible for cancer initiation or progression. While several efforts have been made to predict the locations of single nucleotide variants (SNVs) at miRNA target sites and associate them with cancer risk and susceptibility, there have been few direct assessments of SNVs in both mature miRNAs and their target sites to assess their impact on miRNA function in cancers. METHODS: Using genome-wide target capture of miRNAs and miRNA-binding sites followed by deep sequencing in prostate cancer cell lines, here we identified prostate cancer-specific SNVs in mature miRNAs and their target binding sites. RESULTS: SNV rs9860655 in the mature sequence of miR-570 was not present in benign prostate hyperplasia (BPH) tissue or cell lines but was detectable in clinical prostate cancer tissue samples and adjacent normal tissue. SLC45A3 (prostein), a putative oncogene target of miR-1178, was highly upregulated in PC3 cells harboring an miR-1178 seed sequence SNV. Finally, systematic assessment of losses and gains of miRNA targets through 3’UTR SNVs revealed SNV-associated changes in target oncogene and tumor suppressor gene expression that might be associated with prostate carcinogenesis. CONCLUSIONS: This study provides proof-of-principle that SNVs in mature miRNAs, their seed sequences, and at miRNA target sites are present in prostate cancer and might impact oncogenes and tumor suppressor genes' expression implicated in prostate carcinogenesis. Further functional validation is now required to assess whether these SNVs represent regulatory quantitative trait loci that participate in prostate cancer development. Source of Funding: This work was supported by National Institutes of Health grant NCI 5P30CA030199, Florida Department of Health, Bankhead-Coley Cancer Research Program 5BC08 and International Prostate Cancer Foundation (IPCF) to R.J.P © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e612-e613 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bongyong Lee More articles by this author Jian-Liang Li More articles by this author John Marchica More articles by this author Mark Mercola More articles by this author Vipul Patel More articles by this author Ranjan Perera More articles by this author Expand All Advertisement Loading ...