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Charles E Massie Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK

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Inmaculada Spiteri Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK

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Helen Ross-Adams Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK

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Hayley Luxton Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK

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Jonathan Kay Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK

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Hayley C Whitaker Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK

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Mark J Dunning Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK

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Alastair D Lamb Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK

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Antonio Ramos-Montoya Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK

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Daniel S Brewer Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK

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Colin S Cooper Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK

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Rosalind Eeles Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK

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UK Prostate ICGC Group
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Anne Y Warren Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK

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Simon Tavaré Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK

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David E Neal Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK
Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK

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Andy G Lynch Cancer Research UK Cambridge Institute, Division of Genetics and Epidemiology, Department of Biological Sciences and School of Medicine, Royal Marsden NHS Foundation Trust, Departments of Pathology, Urology, Surgical Oncology, University of Cambridge, Cambridge, CB2 0RE, UK

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prostate cancer and AR signalling ( Ramos-Montoya et al . 2014 ). Herein, we characterise an epigenetic alteration at the promoter of the related HES5 gene, which has been recently reported in a panel of genes that showed promise as a prostate cancer

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James Yao University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Abhishek Garg Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA

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David Chen Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA

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Jaume Capdevila Vall d’Hebron University Hospital, Vall Hebron Institute of Oncology (VHIO), Autonomous University of Barcelona, Barcelona, Spain

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Paul Engstrom Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

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Rodney Pommier Oregon Health and Science University, Portland, Oregon, USA

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Eric Van Cutsem University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven, Belgium

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Simron Singh Odette Cancer Center, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada

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Nicola Fazio European Institute of Oncology, Milan, Italy

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Wei He Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA

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Markus Riester Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA

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Parul Patel Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA

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Maurizio Voi Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA

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Michael Morrissey Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA

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Marianne Pavel University of Erlangen-Nuremberg, Erlangen, Germany

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Matthew Helmut Kulke Dana Farber Cancer Institute, Boston, Massachusetts, USA

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Communications 5 3518 . ( https://doi.org/10.1038/ncomms4518 ) 24670920 10.1038/ncomms4518 Frampton GM Fichtenholtz A Otto GA Wang K Downing SR He J Schnall-Levin M White J Sanford EM An P , et al . 2013 Development and validation of a clinical cancer

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Lei Qiao Department of Breast and Thyroid Surgery, Xinjiang Medical University Affiliated Tumor Hospital, Urumqi, Xinjiang Uygur Autonomous Region, China

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Chao Dong Department of Breast and Thyroid Surgery, Xinjiang Medical University Affiliated Tumor Hospital, Urumqi, Xinjiang Uygur Autonomous Region, China

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Wenlei Jia Department of Breast and Thyroid Surgery, Xinjiang Medical University Affiliated Tumor Hospital, Urumqi, Xinjiang Uygur Autonomous Region, China

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Gang Sun Department of Breast and Thyroid Surgery, Xinjiang Medical University Affiliated Tumor Hospital, Urumqi, Xinjiang Uygur Autonomous Region, China

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miRNA is dysregulated in various cancers and plays roles as either oncogenes or tumor suppressors, which are tightly related to tumor development and occurrence ( Calin & Croce 2006 ), as well as chemoresistance ( Ashrafizadeh et al. 2020 a ). Rab5

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Gina Chia-Yi Chu Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of

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Haiyen E Zhau Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of

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Ruoxiang Wang Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of

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André Rogatko Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of
Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of

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Xu Feng Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of

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Majd Zayzafoon Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of

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Youhua Liu Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of

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Mary C Farach-Carson Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of

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Sungyong You Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of
Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of

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Jayoung Kim Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of
Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of

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Michael R Freeman Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of
Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of
Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of

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Leland W K Chung Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of
Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of

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established by our laboratory ( Xu et al . 2006 ) represent stages of human PCa progression. They were maintained in T-medium (Invitrogen) supplemented with 5% FBS. LNCaP and LNCaP Neo/RANKL were maintained in RPMI-1640 supplemented with 10% FBS. RAW264

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Salma Kaochar Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
Dan L. Duncan Comprehensive Cancer Center, Houston, Texas, USA
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA

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Aleksandra Rusin Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA

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Christopher Foley Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA

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Kimal Rajapakshe Dan L. Duncan Comprehensive Cancer Center, Houston, Texas, USA
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA

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Matthew Robertson Dan L. Duncan Comprehensive Cancer Center, Houston, Texas, USA
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA

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Darlene Skapura Department of Medicine, Baylor College of Medicine, Houston, Texas, USA

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Cammy Mason Department of Medicine, Baylor College of Medicine, Houston, Texas, USA

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Karen Berman De Ruiz Department of Medicine, Baylor College of Medicine, Houston, Texas, USA

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Alexey Mikhailovich Tyryshkin Department of Medicine, Baylor College of Medicine, Houston, Texas, USA

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Jenny Deng Department of Medicine, Baylor College of Medicine, Houston, Texas, USA

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Jin Na Shin Department of Medicine, Baylor College of Medicine, Houston, Texas, USA

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Warren Fiskus Department of Medicine, Baylor College of Medicine, Houston, Texas, USA

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Jianrong Dong Dan L. Duncan Comprehensive Cancer Center, Houston, Texas, USA
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA

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Shixia Huang Dan L. Duncan Comprehensive Cancer Center, Houston, Texas, USA
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA
Department of Education, Innovation, and Technology, Baylor College of Medicine, Houston, Texas, USA

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Nora M Navone Division of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas Anderson Cancer Center, Houston, Texas, USA

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Christel M Davis Avera Institute for Human Genetics, Sioux Falls, South Dakota, USA

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Erik A Ehli Avera Institute for Human Genetics, Sioux Falls, South Dakota, USA

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Cristian Coarfa Dan L. Duncan Comprehensive Cancer Center, Houston, Texas, USA
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA

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Nicholas Mitsiades Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
Dan L. Duncan Comprehensive Cancer Center, Houston, Texas, USA
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA

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(Biorad). Total protein lysate (40 μg) was loaded into 8.5% polyacrylamide gels or NuPage 4–12% Bis-Tris gels and transferred as previously described ( He et al. 2014 ). Images were acquired using an infrared scanner (Odyssey (LiCoR), Lincoln, NE) and

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K M Biernacka IGFs & Metabolic Endocrinology Group, School of Clinical Sciences, Learning & Research Building, Southmead Hospital, Bristol, UK

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R A Persad Department of Urology, Southmead Hospital, Bristol, UK

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A Bahl Department of Clinical Oncology, Bristol Haematology and Oncology Centre, University Hospitals Bristol, Bristol, UK

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D Gillatt Department of Urology, Southmead Hospital, Bristol, UK

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J M P Holly IGFs & Metabolic Endocrinology Group, School of Clinical Sciences, Learning & Research Building, Southmead Hospital, Bristol, UK

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C M Perks IGFs & Metabolic Endocrinology Group, School of Clinical Sciences, Learning & Research Building, Southmead Hospital, Bristol, UK

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( Murtola et al . 2008 , Wright & Stanford 2009 ) and improved survival in prostate cancer patients ( He et al . 2011 ). The anticancer effects of metformin could be mediated by a canonical pathway involving the activation of AMP-activated protein

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Yuet-Kin Leung Division of Environmental Genetics and Molecular Toxicology, Division of Epidemiology and Biostatistics, Center for Environmental Genetics, Cancer Center, Department of Pathology, Department of Pathology and Laboratory Medicine, Department of Environmental Health
Division of Environmental Genetics and Molecular Toxicology, Division of Epidemiology and Biostatistics, Center for Environmental Genetics, Cancer Center, Department of Pathology, Department of Pathology and Laboratory Medicine, Department of Environmental Health
Division of Environmental Genetics and Molecular Toxicology, Division of Epidemiology and Biostatistics, Center for Environmental Genetics, Cancer Center, Department of Pathology, Department of Pathology and Laboratory Medicine, Department of Environmental Health

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Hung-Ming Lam Division of Environmental Genetics and Molecular Toxicology, Division of Epidemiology and Biostatistics, Center for Environmental Genetics, Cancer Center, Department of Pathology, Department of Pathology and Laboratory Medicine, Department of Environmental Health

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Shulin Wu Division of Environmental Genetics and Molecular Toxicology, Division of Epidemiology and Biostatistics, Center for Environmental Genetics, Cancer Center, Department of Pathology, Department of Pathology and Laboratory Medicine, Department of Environmental Health

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Dan Song Division of Environmental Genetics and Molecular Toxicology, Division of Epidemiology and Biostatistics, Center for Environmental Genetics, Cancer Center, Department of Pathology, Department of Pathology and Laboratory Medicine, Department of Environmental Health

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Linda Levin Division of Environmental Genetics and Molecular Toxicology, Division of Epidemiology and Biostatistics, Center for Environmental Genetics, Cancer Center, Department of Pathology, Department of Pathology and Laboratory Medicine, Department of Environmental Health

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Liang Cheng Division of Environmental Genetics and Molecular Toxicology, Division of Epidemiology and Biostatistics, Center for Environmental Genetics, Cancer Center, Department of Pathology, Department of Pathology and Laboratory Medicine, Department of Environmental Health

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Chin-Lee Wu Division of Environmental Genetics and Molecular Toxicology, Division of Epidemiology and Biostatistics, Center for Environmental Genetics, Cancer Center, Department of Pathology, Department of Pathology and Laboratory Medicine, Department of Environmental Health

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Shuk-Mei Ho Division of Environmental Genetics and Molecular Toxicology, Division of Epidemiology and Biostatistics, Center for Environmental Genetics, Cancer Center, Department of Pathology, Department of Pathology and Laboratory Medicine, Department of Environmental Health
Division of Environmental Genetics and Molecular Toxicology, Division of Epidemiology and Biostatistics, Center for Environmental Genetics, Cancer Center, Department of Pathology, Department of Pathology and Laboratory Medicine, Department of Environmental Health
Division of Environmental Genetics and Molecular Toxicology, Division of Epidemiology and Biostatistics, Center for Environmental Genetics, Cancer Center, Department of Pathology, Department of Pathology and Laboratory Medicine, Department of Environmental Health

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addition to the wild-type ERβ or ERβ1, four spliced variants designated as ERβ2–5 have been identified ( Moore et al . 1998 ). The ERβ2–5 isoforms share the first four functional domains with ERβ1, but each has a unique activation function 2 (AF2) domain

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Kreepa G Kooblall OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK

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Victoria J Stokes OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK

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Omair A Shariq OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK

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Katherine A English OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK

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Mark Stevenson OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK

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John Broxholme Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK

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Benjamin Wright Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK

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Helen E Lockstone Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK

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David Buck Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK

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Simona Grozinsky-Glasberg Neuroendocrine Tumor Unit, ENETS Center of Excellence, Endocrinology & Metabolism Department, Hadassah Medical Center and Faculty of Medicine, The Hebrew University of Jerusalem, Israel

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Christopher J Yates OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK

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Rajesh V Thakker OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK
Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, UK

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Kate E Lines OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK

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screening for tumours, from as young as 5 years of age. Current clinical guidelines recommend annual surveillance for tumours by biochemical analyses (e.g. calcium, fasting glucose and hormones such as insulin, gastrin and prolactin) and radiological

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Xiaoli Liu Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Changchun, Jilin, China

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Chunhai Zhang Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Changchun, Jilin, China

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Xiaomiao Wang Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Changchun, Jilin, China

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Can Cui Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Changchun, Jilin, China

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Hanwen Cui Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Changchun, Jilin, China

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Baishu Zhu Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Changchun, Jilin, China

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Anqi Chen Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Changchun, Jilin, China

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Lu Zhang Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Changchun, Jilin, China

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Jingwei Xin Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Changchun, Jilin, China

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Qingfeng Fu Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Changchun, Jilin, China

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Gianlorenzo Dionigi Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
Division of Surgery, Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy

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Hui Sun Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Changchun, Jilin, China

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He S Yang Q Guo W Lai Y Du H Peng X 2019 Copy number gain of ZEB1 mediates a double-negative feedback loop with miR-33a-5p that regulates EMT and bone metastasis of prostate cancer dependent on TGF-beta signaling . Theranostics 9 6063

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Andrew G Gianoukakis Los Angeles Biomedical Research Institute and Division of Endocrinology and Metabolism, Department of Medicine at Harbor-UCLA Medical Center, Torrance, California, USA
David Geffen School of Medicine, University of California – Los Angeles, Los Angeles, California, USA

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Corina E Dutcus Eisai Inc., Woodcliff Lake, New Jersey, USA

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Nicolas Batty Eisai Inc., Woodcliff Lake, New Jersey, USA

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Matthew Guo Eisai Inc., Woodcliff Lake, New Jersey, USA

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Mahadi Baig Eisai Inc., Woodcliff Lake, New Jersey, USA

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with greater disease burden (tumor size ≤35 mm: 44.3 months; 35–60 mm: 27.5 months; 60–92 mm: 18.0 months; >92 mm: 15.7 months), patients with liver metastasis (yes: 15.7 months; no: 30.5 months) and patients with brain metastasis (yes: 9.3 months; no

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