| Literature DB >> 26080435 |
Ahmad Salameh1, Alessandro K Lee2, Marina Cardó-Vila3, Diana N Nunes4, Eleni Efstathiou5, Fernanda I Staquicini3, Andrey S Dobroff3, Serena Marchiò6, Nora M Navone5, Hitomi Hosoya2, Richard C Lauer7, Sijin Wen8, Carolina C Salmeron3, Anh Hoang5, Irene Newsham2, Leandro A Lima9, Dirce M Carraro9, Salvatore Oliviero10, Mikhail G Kolonin11, Richard L Sidman12, Kim-Anh Do8, Patricia Troncoso13, Christopher J Logothetis5, Ricardo R Brentani9, George A Calin14, Webster K Cavenee15, Emmanuel Dias-Neto16, Renata Pasqualini17, Wadih Arap18.
Abstract
Prostate cancer antigen 3 (PCA3) is the most specific prostate cancer biomarker but its function remains unknown. Here we identify PRUNE2, a target protein-coding gene variant, which harbors the PCA3 locus, thereby classifying PCA3 as an antisense intronic long noncoding (lnc)RNA. We show that PCA3 controls PRUNE2 levels via a unique regulatory mechanism involving formation of a PRUNE2/PCA3 double-stranded RNA that undergoes adenosine deaminase acting on RNA (ADAR)-dependent adenosine-to-inosine RNA editing. PRUNE2 expression or silencing in prostate cancer cells decreased and increased cell proliferation, respectively. Moreover, PRUNE2 and PCA3 elicited opposite effects on tumor growth in immunodeficient tumor-bearing mice. Coregulation and RNA editing of PRUNE2 and PCA3 were confirmed in human prostate cancer specimens, supporting the medical relevance of our findings. These results establish PCA3 as a dominant-negative oncogene and PRUNE2 as an unrecognized tumor suppressor gene in human prostate cancer, and their regulatory axis represents a unique molecular target for diagnostic and therapeutic intervention.Entities:
Keywords: ADAR; PCA3; PRUNE2; long noncoding RNA; prostate cancer
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Year: 2015 PMID： 26080435 PMCID： PMC4500257 DOI： 10.1073/pnas.1507882112
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205