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Re: Integrative Analyses Reveal a Long Noncoding RNA-Mediated Sponge Regulatory Network in Prostate Cancer
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Uro-Science Re: Activation of Notch1 Synergizes with Multiple Pathways in Promoting Castration-Resistant Prostate Cancer T. Stoyanova, M. Riedinger, S. Lin, C. M. Faltermeier, B. A. Smith, K. X. Zhang, C. C. Going, A. S. Goldstein, J. K. Lee, J. M. Drake, M. A. Rice, E. C. Hsu, B. Nowroozizadeh, B. Castor, S. Y. Orellana, S. M. Blum, D. Cheng, K. J. Pienta, R. E. Reiter, S. J. Pitteri, J. Huang and O. N. Witte Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, Department of Microbiology, Immunology and Molecular Genetics, Department of Molecular and Medical Pharmacology, Department of Urology, Department of Biological Chemistry, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Department of Molecular, Cell and Developmental Biology, Division of Hematology and Medical Oncology, Department of Pathology and Laboratory Medicine, and Howard Hughes Medical Institute, University of California, Los Angeles and Department of Pathology, University of California, Irvine, California, Rutgers Cancer Institute of New Jersey and Department of Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey, Department of Internal Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, and Department of Pathology, Duke University School of Medicine, Durham, North Carolina Proc Natl Acad Sci U S A 2016; 113: E6457eE6466. doi: 10.1073/pnas.1614529113
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27694579 Editorial Comment: The authors report significantly increased levels of nuclear Notch1 intracellular domain in hormone naive, high risk prostate cancer and nearly all metastatic castration resistant prostate cancer specimens but not in benign tissues or in low or intermediate risk localized prostate cancer. Although overexpression of Notch1 intracellular domain alone was not sufficient to drive prostate tumorigenesis, Notch1 intracellular domain in combination with components of pathways commonly altered in early prostate cancer, such as myristoylated AKT, Myc and Ras/Raf/ MAPK, promoted development of aggressive prostate adenocarcinoma and progression to castration resistant prostate cancer. Consistent with their aggressiveness, these tumors displayed an epithelialto-mesenchymal transition phenotype, high self-renewal and the potential for metastatic colonization. Tumors driven by Notch1 intracellular domain in combination with myristoylated AKT, Myc and the Ras/Raf/MAPK pathway are also resistant to androgen deprivation. The results indicate that Notch1 receptor signaling has a central role in the development and progression of prostate cancer, and may serve as a rational therapeutic target in high risk prostate cancer and metastatic castration resistant prostate cancer. Anthony Atala, MD
Suggested Reading Angulo JC, Andres G, Ashour N et al: Development of castration resistant prostate cancer can be predicted by a DNA hypermethylation profile. J Urol 2016; 195: 619. Crawford ED, Higano CS, Shore ND et al: Treating patients with metastatic castration resistant prostate cancer: a comprehensive review of available therapies. J Urol 2015; 194: 1537.
Re: Integrative Analyses Reveal a Long Noncoding RNA-Mediated Sponge Regulatory Network in Prostate Cancer Z. Du, T. Sun, E. Hacisuleyman, T. Fei, X. Wang, M. Brown, J. L. Rinn, M. G. Lee, Y. Chen, P. W. Kantoff and X. S. Liu 0022-5347/17/1973-0001/0 THE JOURNAL OF UROLOGY® Ó 2017 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2016.12.030 Vol. 197, 1-3, March 2017 Printed in U.S.A.
www.jurology.com Dochead: Urological Survey
LIT 5.4.0 DTD JURO14258_proof 15 December 2016 6:06 pm EO:
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Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital and Department of Bioinformatics, School of Life Sciences and Technology, Tongji University, Shanghai, China, Department of Medical Oncology, Center for Functional Cancer Epigenetics, and Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School and Harvard School of Public Health, and Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Department of Pathology, University of Massachusetts Medical School, Worcester, and Departments of Molecular and Cellular Biology, and Stem Cell and Regenerative Biology, Harvard University and Broad Institute of Massachusetts Institute of Technology, Cambridge, Massachusetts, Department of Bioinformatics and Computational Biology, Division of Quantitative Sciences, University of Texas MD Anderson Cancer Center, Houston, Texas, and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York Nat Commun 2016; 7: 10982. doi: 10.1038/ncomms10982
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26975529 Editorial Comment: Approximately 70% of the human genome is transcribed but less than 2% of the genome encodes protein. On the basis of size, noncoding RNAs can be classified as small (r200 base pairs) or long noncoding RNAs (lncRNAs, 4,200 base pairs). The human genome encodes around 10,000 lncRNA genes and, similar to protein coding genes, some lncRNAs can mediate oncogenesis or tumor suppression and, therefore, are a potential new class of cancer therapeutic targets. Despite this relevance to cancer, only a handful of lncRNAs have been functionally characterized. The prevalence and functional significance of lncRNA mediated sponge regulation and the relevant targets in human cancer are unclear. To address these questions, the authors systematically identified an lncRNA mediated sponge regulatory network of protein coding driver genes in prostate cancer by integrating sequence features and gene expression of lncRNAs and protein coding genes in tumors. The authors also validated the tumor suppressive function of 2 lncRNAs predicted to serve as microRNA sponges and positively regulate PTEN expression. The study shows a prevalent and complex lncRNA mediated sponge regulatory mechanism that may significantly contribute to the aberrant expression of critical protein coding driver genes in prostate cancer. Those sp-lncRNAs may have oncogenic or tumor suppressive function, and perturbation of the lncRNA mediated sponge regulation might be exploited for cancer therapy. The study also suggests the vast functional space of lncRNAs as microRNA sponges in cancer pathogenesis and the plasticity of lncRNAs in performing multiple functions. Anthony Atala, MD
Suggested Reading Ren S, Liu Y, Xu W et al: Long noncoding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer. J Urol 2013; 190: 2278.
Re: Integrated Classification of Prostate Cancer Reveals a Novel Luminal Subtype with Poor Outcome S. You, B. S. Knudsen, N. Erho, M. Alshalalfa, M. Takhar, H. Al-Deen Ashab, E. Davicioni, R. J. Karnes, E. A. Klein, R. B. Den, A. E. Ross, E. M. Schaeffer, I. P. Garraway, J. Kim and M. R. Freeman Division of Cancer Biology and Therapeutics, Departments of Surgery and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center and Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, California, Department of Urology, Mayo Clinic, Rochester, Minnesota, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, Department of Urology, Northwestern University, Chicago, Illinois, and GenomeDx Biosciences, Inc., Vancouver, British Columbia, Canada Cancer Res 2016; 76: 4948e4958. doi:10.1158/0008-5472.CAN-16-0902
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27302169 Editorial Comment: The authors present the results of an integrated analysis of a large set of transcriptome data from more than 4,600 clinical prostate cancer specimens. The study showed that RNA expression data can be used to categorize prostate cancer tumors into 3 distinct subtypes based on molecular pathway representation encompassing molecular lesions and cellular features related to prostate cancer biology. Application of this subtyping scheme to 10 independent cohorts and a wide range of preclinical prostate cancer models strongly suggests that the subtypes defined originate from inherent differences in prostate cancer origins and/or biological features. This novel prostate cancer classification scheme can be useful for detection of aggressive tumors using tissue as well as blood from patients with progressing disease. It also provides a starting point for development of subtype specific treatment strategies and companion diagnostics. Anthony Atala, MD Dochead: Urological Survey
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Uro-Science Re: Activation of Notch1 Synergizes with Multiple Pathways in Promoting Castration-Resistant Prostate Cancer T. Stoyanova, M. Riedinger, S. Lin, C. M. Faltermeier, B. A. Smith, K. X. Zhang, C. C. Going, A. S. Goldstein, J. K. Lee, J. M. Drake, M. A. Rice, E. C. Hsu, B. Nowroozizadeh, B. Castor, S. Y. Orellana, S. M. Blum, D. Cheng, K. J. Pienta, R. E. Reiter, S. J. Pitteri, J. Huang and O. N. Witte Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, Department of Microbiology, Immunology and Molecular Genetics, Department of Molecular and Medical Pharmacology, Department of Urology, Department of Biological Chemistry, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Department of Molecular, Cell and Developmental Biology, Division of Hematology and Medical Oncology, Department of Pathology and Laboratory Medicine, and Howard Hughes Medical Institute, University of California, Los Angeles and Department of Pathology, University of California, Irvine, California, Rutgers Cancer Institute of New Jersey and Department of Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey, Department of Internal Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, and Department of Pathology, Duke University School of Medicine, Durham, North Carolina Proc Natl Acad Sci U S A 2016; 113: E6457eE6466. doi: 10.1073/pnas.1614529113
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27694579 Editorial Comment: The authors report significantly increased levels of nuclear Notch1 intracellular domain in hormone naive, high risk prostate cancer and nearly all metastatic castration resistant prostate cancer specimens but not in benign tissues or in low or intermediate risk localized prostate cancer. Although overexpression of Notch1 intracellular domain alone was not sufficient to drive prostate tumorigenesis, Notch1 intracellular domain in combination with components of pathways commonly altered in early prostate cancer, such as myristoylated AKT, Myc and Ras/Raf/ MAPK, promoted development of aggressive prostate adenocarcinoma and progression to castration resistant prostate cancer. Consistent with their aggressiveness, these tumors displayed an epithelialto-mesenchymal transition phenotype, high self-renewal and the potential for metastatic colonization. Tumors driven by Notch1 intracellular domain in combination with myristoylated AKT, Myc and the Ras/Raf/MAPK pathway are also resistant to androgen deprivation. The results indicate that Notch1 receptor signaling has a central role in the development and progression of prostate cancer, and may serve as a rational therapeutic target in high risk prostate cancer and metastatic castration resistant prostate cancer. Anthony Atala, MD
Suggested Reading Angulo JC, Andres G, Ashour N et al: Development of castration resistant prostate cancer can be predicted by a DNA hypermethylation profile. J Urol 2016; 195: 619. Crawford ED, Higano CS, Shore ND et al: Treating patients with metastatic castration resistant prostate cancer: a comprehensive review of available therapies. J Urol 2015; 194: 1537.
Re: Integrative Analyses Reveal a Long Noncoding RNA-Mediated Sponge Regulatory Network in Prostate Cancer Z. Du, T. Sun, E. Hacisuleyman, T. Fei, X. Wang, M. Brown, J. L. Rinn, M. G. Lee, Y. Chen, P. W. Kantoff and X. S. Liu 0022-5347/17/1973-0001/0 THE JOURNAL OF UROLOGY® Ó 2017 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2016.12.030 Vol. 197, 1-3, March 2017 Printed in U.S.A.
www.jurology.com Dochead: Urological Survey
LIT 5.4.0 DTD JURO14258_proof 15 December 2016 6:06 pm EO:
j
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URO-SCIENCE
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115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171
Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital and Department of Bioinformatics, School of Life Sciences and Technology, Tongji University, Shanghai, China, Department of Medical Oncology, Center for Functional Cancer Epigenetics, and Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School and Harvard School of Public Health, and Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Department of Pathology, University of Massachusetts Medical School, Worcester, and Departments of Molecular and Cellular Biology, and Stem Cell and Regenerative Biology, Harvard University and Broad Institute of Massachusetts Institute of Technology, Cambridge, Massachusetts, Department of Bioinformatics and Computational Biology, Division of Quantitative Sciences, University of Texas MD Anderson Cancer Center, Houston, Texas, and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York Nat Commun 2016; 7: 10982. doi: 10.1038/ncomms10982
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26975529 Editorial Comment: Approximately 70% of the human genome is transcribed but less than 2% of the genome encodes protein. On the basis of size, noncoding RNAs can be classified as small (r200 base pairs) or long noncoding RNAs (lncRNAs, 4,200 base pairs). The human genome encodes around 10,000 lncRNA genes and, similar to protein coding genes, some lncRNAs can mediate oncogenesis or tumor suppression and, therefore, are a potential new class of cancer therapeutic targets. Despite this relevance to cancer, only a handful of lncRNAs have been functionally characterized. The prevalence and functional significance of lncRNA mediated sponge regulation and the relevant targets in human cancer are unclear. To address these questions, the authors systematically identified an lncRNA mediated sponge regulatory network of protein coding driver genes in prostate cancer by integrating sequence features and gene expression of lncRNAs and protein coding genes in tumors. The authors also validated the tumor suppressive function of 2 lncRNAs predicted to serve as microRNA sponges and positively regulate PTEN expression. The study shows a prevalent and complex lncRNA mediated sponge regulatory mechanism that may significantly contribute to the aberrant expression of critical protein coding driver genes in prostate cancer. Those sp-lncRNAs may have oncogenic or tumor suppressive function, and perturbation of the lncRNA mediated sponge regulation might be exploited for cancer therapy. The study also suggests the vast functional space of lncRNAs as microRNA sponges in cancer pathogenesis and the plasticity of lncRNAs in performing multiple functions. Anthony Atala, MD
Suggested Reading Ren S, Liu Y, Xu W et al: Long noncoding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer. J Urol 2013; 190: 2278.
Re: Integrated Classification of Prostate Cancer Reveals a Novel Luminal Subtype with Poor Outcome S. You, B. S. Knudsen, N. Erho, M. Alshalalfa, M. Takhar, H. Al-Deen Ashab, E. Davicioni, R. J. Karnes, E. A. Klein, R. B. Den, A. E. Ross, E. M. Schaeffer, I. P. Garraway, J. Kim and M. R. Freeman Division of Cancer Biology and Therapeutics, Departments of Surgery and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center and Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, California, Department of Urology, Mayo Clinic, Rochester, Minnesota, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, Department of Urology, Northwestern University, Chicago, Illinois, and GenomeDx Biosciences, Inc., Vancouver, British Columbia, Canada Cancer Res 2016; 76: 4948e4958. doi:10.1158/0008-5472.CAN-16-0902
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27302169 Editorial Comment: The authors present the results of an integrated analysis of a large set of transcriptome data from more than 4,600 clinical prostate cancer specimens. The study showed that RNA expression data can be used to categorize prostate cancer tumors into 3 distinct subtypes based on molecular pathway representation encompassing molecular lesions and cellular features related to prostate cancer biology. Application of this subtyping scheme to 10 independent cohorts and a wide range of preclinical prostate cancer models strongly suggests that the subtypes defined originate from inherent differences in prostate cancer origins and/or biological features. This novel prostate cancer classification scheme can be useful for detection of aggressive tumors using tissue as well as blood from patients with progressing disease. It also provides a starting point for development of subtype specific treatment strategies and companion diagnostics. Anthony Atala, MD Dochead: Urological Survey
LIT 5.4.0 DTD JURO14258_proof 15 December 2016 6:06 pm EO:
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