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

Salameh, Ahmad ; Alessandro K. Lee ; Marina CardoÌ-Vila ; Diana N. Nunes ; Eleni Efstathiou ; Fernanda I. Staquicini ; Andrey S. Dobroff ; Serena MarchioÌoÌ ; Nora M. Navone ; Hitomi Hosoya ; Richard C. Lauer ; Sijin Wen ; Carolina C. Salmeron ; Anh Hoang ; Irene Newsham ; Leandro A. Lima ; Dirce M. Carraro ; Salvatore Oliviero ; Mikhail G. Kolonin ; Richard L. Sidman ; Kim-Anh Do ; Patricia Troncoso ; Christopher J. Logothetis ; Ricardo R. Brentani ; George A. Calin ; Webster K. Cavenee ; Emmanuel Dias-Neto ; Renata Pasqualini ; Wadih Arap

Proceedings of the National Academy of Sciences - PNAS, 2015-07, Vol.112 (27), p.8403-8408 [Periódico revisado por pares]

United States: National Academy of Sciences

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Título:
PRUNE2 is a human prostate cancer suppressor regulated by the intronic long noncoding RNA PCA3
Autor: Salameh, Ahmad ; Alessandro K. Lee ; Marina CardoÌ-Vila ; Diana N. Nunes ; Eleni Efstathiou ; Fernanda I. Staquicini ; Andrey S. Dobroff ; Serena MarchioÌoÌ ; Nora M. Navone ; Hitomi Hosoya ; Richard C. Lauer ; Sijin Wen ; Carolina C. Salmeron ; Anh Hoang ; Irene Newsham ; Leandro A. Lima ; Dirce M. Carraro ; Salvatore Oliviero ; Mikhail G. Kolonin ; Richard L. Sidman ; Kim-Anh Do ; Patricia Troncoso ; Christopher J. Logothetis ; Ricardo R. Brentani ; George A. Calin ; Webster K. Cavenee ; Emmanuel Dias-Neto ; Renata Pasqualini ; Wadih Arap
Assuntos: ADAR ; adenosine deaminase ; Adenosine Deaminase - genetics ; Adenosine Deaminase - metabolism ; Animals ; Antigens ; Antigens, Neoplasm - genetics ; Antigens, Neoplasm - metabolism ; Biological Sciences ; Biomarkers ; Cell Line, Tumor ; cell proliferation ; Cells ; double-stranded RNA ; Gene Expression Regulation, Neoplastic ; HEK293 Cells ; HeLa Cells ; Humans ; Immunoblotting ; Introns - genetics ; loci ; long noncoding RNA ; Male ; MCF-7 Cells ; mice ; Mice, SCID ; Molecular Sequence Data ; neoplasm cells ; Neoplasm Proteins - genetics ; Neoplasm Proteins - metabolism ; non-coding RNA ; oncogenes ; PCA3 ; Prostate cancer ; prostatic neoplasms ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - metabolism ; Prostatic Neoplasms - pathology ; Protein Binding ; PRUNE2 ; Reverse Transcriptase Polymerase Chain Reaction ; Ribonucleic acid ; RNA ; RNA editing ; RNA Interference ; RNA Precursors - genetics ; RNA Precursors - metabolism ; RNA, Long Noncoding - genetics ; RNA, Long Noncoding - metabolism ; Rodents ; tumor suppressor genes ; Tumor Suppressor Proteins - genetics ; Tumor Suppressor Proteins - metabolism ; Tumors ; Xenograft Model Antitumor Assays - methods
É parte de: Proceedings of the National Academy of Sciences - PNAS, 2015-07, Vol.112 (27), p.8403-8408
Notas: http://dx.doi.org/10.1073/pnas.1507882112
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4Present address: School of Public Health, West Virginia University, Morgantown, WV 26506.
7E.D.-N., R.P., and W.A. contributed equally to this work.
Edited by Owen N. Witte, Howard Hughes Medical Institute, University of California, Los Angeles, CA, and approved May 13, 2015 (received for review March 16, 2015)
Author contributions: A.S., A.K.L., M.C.-V., D.N.N., E.E., F.I.S., A.S.D., E.D.-N., R.P., and W.A. designed research; A.S., A.K.L., M.C.-V., D.N.N., F.I.S., A.S.D., H.H., A.H., and E.D.-N. performed research; E.E., S.M., N.M.N., R.C.L., S.W., C.C.S., D.M.C., S.O., M.G.K., R.L.S., K.-A.D., P.T., C.J.L., R.R.B., and G.A.C. contributed new reagents/analytic tools; A.S., A.K.L., M.C.-V., D.N.N., E.E., F.I.S., A.S.D., H.H., R.C.L., S.W., C.C.S., I.N., L.A.L., M.G.K., R.L.S., K.-A.D., P.T., C.J.L., R.R.B., G.A.C., W.K.C., E.D.-N., R.P., and W.A. analyzed data; A.S., A.K.L., M.C.-V., D.N.N., E.E., F.I.S., A.S.D., R.L.S., G.A.C., W.K.C., E.D.-N., R.P., and W.A. wrote the paper; and E.D.-N., R.P., and W.A. jointly supervised this project.
3Present address: The US Naval Hospital Yokosuka, PSC 475 FPO AP 96350-9998, Japan.
2Present address: Janssen-Cilag SpA., Cologno Monzese, Milan 20093, Italy.
5Deceased November 29, 2011.
1A.S. and A.K.L. contributed equally to this work.
Descrição: 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.
Editor: United States: National Academy of Sciences
Idioma: Inglês

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

United States: National Academy of Sciences

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