Dataset Information

PRUNE2 is a human prostate cancer suppressor regulated by the intronic long noncoding RNA PCA3.

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.

SUBMITTER: Salameh A

PROVIDER: S-EPMC4500257 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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PRUNE2 is a human prostate cancer suppressor regulated by the intronic long noncoding RNA PCA3.

Salameh Ahmad A Lee Alessandro K AK Cardó-Vila Marina M Nunes Diana N DN Efstathiou Eleni E Staquicini Fernanda I FI Dobroff Andrey S AS Marchiò Serena S Navone Nora M NM Hosoya Hitomi H Lauer Richard C RC Wen Sijin S Salmeron Carolina C CC Hoang Anh A Newsham Irene I Lima Leandro A LA Carraro Dirce M DM Oliviero Salvatore S Kolonin Mikhail G MG Sidman Richard L RL Do Kim-Anh KA Troncoso Patricia P Logothetis Christopher J CJ Brentani Ricardo R RR Calin George A GA Calin George A GA Cavenee Webster K WK Dias-Neto Emmanuel E Pasqualini Renata R Arap Wadih W

Proceedings of the National Academy of Sciences of the United States of America 20150615 27

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 ...[more]

PMID: 26080435

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Dataset Information

PRUNE2 is a human prostate cancer suppressor regulated by the intronic long noncoding RNA PCA3.

Publications

PRUNE2 is a human prostate cancer suppressor regulated by the intronic long noncoding RNA PCA3.

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