ArticleProceedings of the National Academy of Sciences of the United States of America2015
PRUNE2 is a human prostate cancer suppressor regulated by the intronic long noncoding RNA PCA3.
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Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 1 of them a synthesis that pooled it.
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147citing papers in PubMed, 1 pooled it
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147 citing papers in PubMed, 1 synthesis or guideline pooled it, 278 citations in OpenAlex.
- Transcriptional landscape of PTEN loss in primary prostate cancer.BMC cancer · 2021Pooled it
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- RNA modifications in cancer: regulators of tumor evolution and therapeutic response.Molecular cancer · 2026Review
- The regulatory mechanism and clinical significance of RNA editing in prostate cancer.Current urology · 2026Review
- A dual role of EZH2 in regulating A-to-I RNA editing and mRNA stability through ADAR.Nature communications · 2026Article
- RANBP1 promotes immune evasion in triple-negative breast cancer by suppressing T cell infiltration via the miR-769-5p/PRUNE2 axis.Discover oncology · 2025Article
- Female and male hormonal-dependent malignancies: the role of long non-coding RNAs.Medical oncology (Northwood, London, England) · 2025Review
- Upregulation of PCAT1, PCAT2, and PCAT3 LncRNAs in cervical cancer patients and their diagnostic value.BMC research notes · 2025Article
- Novel lncRNAInternational journal of molecular sciences · 2025Article
- Characterization of RNA editing gene APOBEC3C as a candidate tumor suppressor in prostate cancer.Scientific reports · 2025Article
- MXene and prostate cancer: is there promising news?Nanomedicine (London, England) · 2025Review
- Epigenetic and epitranscriptomic role of lncRNA in carcinogenesis (Review).International journal of oncology · 2025Review
- Long Intergenic Non-Coding RNAs andNon-coding RNA · 2025Review
- Identification of Novel lncRNAs Related to Colorectal Cancer Through Bioinformatics Analysis.BioMed research international · 2025Article
- New biomarkers and multiplex tests for diagnosis of aggressive prostate cancer and therapy management.Frontiers in oncology · 2025Review
- Evaluation of LncRNAs CBR3-AS1 and PCA3 expression in Gastric cancer and their correlation to clinicopathological variables.Genes & cancer · 2025Article
- Advances in A-to-I RNA editing in cancer.Molecular cancer · 2024Review
- Exploring the Role of Long Non-Coding RNAs in Predicting Outcomes for Hepatitis B Patients.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Article
- Genetics of cell-type-specific post-transcriptional gene regulation during human neurogenesis.American journal of human genetics · 2024Article
87 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 9 institutions in 3 countries.
Ahmad SalamehDavid 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;
Alessandro K LeeDavid H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030;
Marina Cardó-VilaDavid 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;
Diana N NunesDavid 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;
Eleni EfstathiouDavid 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;
Fernanda I StaquiciniDavid 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;
Andrey S DobroffDavid 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;
Serena MarchiòCandiolo Cancer Institute and Department of Oncology, University of Turin, Candiolo 10060, Italy;
Nora M NavoneDavid 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;
Hitomi HosoyaDavid H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030;
Richard C LauerUniversity 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;
Sijin WenDepartment of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030;
Carolina C SalmeronDavid 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;
Anh HoangDavid 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;
Irene NewshamDavid H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030;
Leandro A LimaInternational Research Center, A.C. Camargo Cancer Center, São Paulo, SP 01508-010 Brazil;
Dirce M CarraroInternational Research Center, A.C. Camargo Cancer Center, São Paulo, SP 01508-010 Brazil;
Salvatore OlivieroHuman Genetics Foundation, Torino 10126, Italy;
Mikhail G KoloninBrown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030;
Richard L SidmanHarvard Medical School and Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215;
Kim-Anh DoDepartment of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030;
Patricia TroncosoDavid 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;
Christopher J LogothetisDavid 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;
Ricardo R BrentaniInternational Research Center, A.C. Camargo Cancer Center, São Paulo, SP 01508-010 Brazil;
George A CalinDepartment 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;
Webster K CaveneeLudwig 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.
Emmanuel Dias-NetoDavid 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.
Renata PasqualiniDavid 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.
Wadih ArapDavid 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.
The University of Texas MD Anderson Cancer Center · USNew Mexico Cancer Center · USAC Camargo Hospital · BRBrown Foundation · USHarvard University · USItalian institute for Genomic Medicine · ITUniversity of California, San Diego · USUniversity of New Mexico · USUniversity of Turin · IT
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MWest Virginia IDEA-CTRU54GM104942 · NIGMS · WEST VIRGINIA UNIVERSITY · PI Sally Lynn Hodder · 2012 to 2026
$81.0MTransgenic Mouse and Biobank CoreP01CA095616 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DEPINHO, RONALD ANTHONY · 2003 to 2012
$20.3MUniversity of Texas SPORE in Prostate CancerP50CA090270 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LOGOTHETIS, CHRISTOPHER J. · 2001 to 2007
$13.6MNCI NIH HHS CA90270NCI NIH HHS CA95616NCI NIH HHS P01 CA095616NCI NIH HHS P50 CA090270NIGMS NIH HHS U54 GM104942
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.
Indexed as
Adenosine DeaminaseAnimalsAntigens, NeoplasmCell Line, TumorGene Expression Regulation, NeoplasticHEK293 CellsHeLa CellsHumansImmunoblottingIntronsMaleMCF-7 CellsMice, SCIDMolecular Sequence DataNeoplasm ProteinsProstatic NeoplasmsADAR1 protein, mouseAdenosine DeaminaseAntigens, NeoplasmNeoplasm Proteinsprostate cancer antigen 3, humanPRUNE2 protein, humanRNA, Long NoncodingRNA PrecursorsTumor Suppressor ProteinsADARlong noncoding RNAPCA3prostate cancerPRUNE2
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