例如："lncRNA", "apoptosis", "WRKY"

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

Proc. Natl. Acad. Sci. U.S.A.2015 Jul 07;112(27):8403-8. Epub 2015 Jun 15
Ahmad Salameh 1 , Alessandro K Lee 2 , Marina Cardó-Vila 3 , Diana N Nunes 4 , Eleni Efstathiou 5 , Fernanda I Staquicini 3 , Andrey S Dobroff 3 , Serena Marchiò 6 , Nora M Navone 5 , Hitomi Hosoya 2 , Richard C Lauer 7 , Sijin Wen 8 , Carolina C Salmeron 3 , Anh Hoang 5 , Irene Newsham 2 , Leandro A Lima 9 , Dirce M Carraro 9 , Salvatore Oliviero 10 , Mikhail G Kolonin 11 , Richard L Sidman 12 , Kim-Anh Do 8 , Patricia Troncoso 13 , Christopher J Logothetis 5 , Ricardo R Brentani 9 , George A Calin 14 , Webster K Cavenee 15 , Emmanuel Dias-Neto 16 , Renata Pasqualini 17 , Wadih Arap 18
Ahmad Salameh 1 , Alessandro K Lee 2 , Marina Cardó-Vila 3 , Diana N Nunes 4 , Eleni Efstathiou 5 , Fernanda I Staquicini 3 , Andrey S Dobroff 3 , Serena Marchiò 6 , Nora M Navone 5 , Hitomi Hosoya 2 , Richard C Lauer 7 , Sijin Wen 8 , Carolina C Salmeron 3 , Anh Hoang 5 , Irene Newsham 2 , Leandro A Lima 9 , Dirce M Carraro 9 , Salvatore Oliviero 10 , Mikhail G Kolonin 11 , Richard L Sidman 12 , Kim-Anh Do 8 , Patricia Troncoso 13 , Christopher J Logothetis 5 , Ricardo R Brentani 9 , George A Calin 14 , Webster K Cavenee 15 , Emmanuel Dias-Neto 16 , Renata Pasqualini 17 , Wadih Arap 18
+ et al

[No authors listed]

Author information
  • 1 David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030; Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030;
  • 2 David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030;
  • 3 David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030; University of New Mexico Cancer Center, University of New Mexico School of Medicine, Albuquerque, NM 87131; Division of Molecular Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131; Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131;
  • 4 David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030; International Research Center, A.C. Camargo Cancer Center, São Paulo, SP 01508-010 Brazil;
  • 5 David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030; Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030;
  • 6 Candiolo Cancer Institute and Department of Oncology, University of Turin, Candiolo 10060, Italy;
  • 7 University of New Mexico Cancer Center, University of New Mexico School of Medicine, Albuquerque, NM 87131; Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131; Division of Hematology/Oncology, University of New Mexico School of Medicine, Albuquerque, NM 87131;
  • 8 Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030;
  • 9 International Research Center, A.C. Camargo Cancer Center, São Paulo, SP 01508-010 Brazil;
  • 10 Human Genetics Foundation, Torino 10126, Italy;
  • 11 Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030;
  • 12 Harvard Medical School and Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215;
  • 13 David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030; Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030;
  • 14 Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030; Center for RNA Interference and Noncoding RNA, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030;
  • 15 Ludwig Institute for Cancer Research, University of California-San Diego, La Jolla, CA 92093; wcavenee@ucsd.edu emmanuel@cipe.accamargo.org.br rpasqual@salud.unm.edu warap@salud.unm.edu.
  • 16 David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030; International Research Center, A.C. Camargo Cancer Center, São Paulo, SP 01508-010 Brazil; Institute of Psychiatry, University of São Paulo Medical School, São Paulo 01060, Brazil wcavenee@ucsd.edu emmanuel@cipe.accamargo.org.br rpasqual@salud.unm.edu warap@salud.unm.edu.
  • 17 David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030; University of New Mexico Cancer Center, University of New Mexico School of Medicine, Albuquerque, NM 87131; Division of Molecular Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131; Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131; Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030; wcavenee@ucsd.edu emmanuel@cipe.accamargo.org.br rpasqual@salud.unm.edu warap@salud.unm.edu.
  • 18 David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030; University of New Mexico Cancer Center, University of New Mexico School of Medicine, Albuquerque, NM 87131; Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131; Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030; Division of Hematology/Oncology, University of New Mexico School of Medicine, Albuquerque, NM 87131; wcavenee@ucsd.edu emmanuel@cipe.accamargo.org.br rpasqual@salud.unm.edu warap@salud.unm.edu.

摘要

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.

KEYWORDS: ADAR, PCA3, PRUNE2, long noncoding RNA, prostate cancer

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