Literature DB >> 30181389

Synergistic Interaction of HOXB13 and CIP2A Predisposes to Aggressive Prostate Cancer.

Csilla Sipeky1, Ping Gao2, Qin Zhang2, Liang Wang3, Otto Ettala4, Kirsi M Talala5, Teuvo L J Tammela6, Anssi Auvinen7, Fredrik Wiklund8, Gong-Hong Wei9, Johanna Schleutker10,11.   

Abstract

PURPOSE: Distinguishing aggressive prostate cancer from indolent disease improves personalized treatment. Although only few genetic variants are known to predispose to aggressive prostate cancer, synergistic interactions of HOXB13 G84E high-risk prostate cancer susceptibility mutation with other genetic loci remain unknown. The purpose of this study was to examine the interplay of HOXB13 rs138213197 (G84E) and CIP2A rs2278911 (R229Q) germline variants on prostate cancer risk. EXPERIMENTAL
DESIGN: Genotyping was done in Finnish discovery cohort (n = 2,738) and validated in Swedish (n = 3,132) and independent Finnish (n = 1,155) prostate cancer cohorts. Expression pattern analysis was followed by functional studies in prostate cancer cell models.
RESULTS: Interplay of HOXB13 (G84E) and CIP2A (R229Q) variants results in highest observed inherited prostate cancer risk (OR, 21.1; P = 0.000024). In addition, this synergism indicates a significant association of HOXB13 T and CIP2A T dual carriers with elevated risk for high Gleason score (OR, 2.3; P = 0.025) and worse prostate cancer-specific life expectancy (HR, 3.9; P = 0.048), and it is linked with high PSA at diagnosis (OR, 3.30; P = 0.028). Furthermore, combined high expression of HOXB13-CIP2A correlates with earlier biochemical recurrence. Finally, functional experiments showed that ectopic expression of variants stimulates prostate cancer cell growth and migration. In addition, we observed strong chromatin binding of HOXB13 at CIP2A locus and revealed that HOXB13 functionally promotes CIP2A transcription. The study is limited to retrospective Nordic cohorts.
CONCLUSIONS: Simultaneous presence of HOXB13 T and CIP2A T alleles confers for high prostate cancer risk and aggressiveness of disease, earlier biochemical relapse, and lower disease-specific life expectancy. HOXB13 protein binds to CIP2A gene and functionally promotes CIP2A transcription. ©2018 American Association for Cancer Research.

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Year:  2018        PMID： 30181389      PMCID： PMC6719560          DOI： 10.1158/1078-0432.CCR-18-0444

Source DB:  PubMed          Journal:  Clin Cancer Res        ISSN： 1078-0432            Impact factor:   12.531


  48 in total

1.  Comprehensively evaluating cis-regulatory variation in the human prostate transcriptome by using gene-level allele-specific expression.

Authors:  Nicholas B Larson; Shannon McDonnell; Amy J French; Zach Fogarty; John Cheville; Sumit Middha; Shaun Riska; Saurabh Baheti; Asha A Nair; Liang Wang; Daniel J Schaid; Stephen N Thibodeau
Journal:  Am J Hum Genet       Date:  2015-05-14       Impact factor: 11.025

2.  Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study.

Authors:  Zsofia Kote-Jarai; Ali Amin Al Olama; Graham G Giles; Gianluca Severi; Johanna Schleutker; Maren Weischer; Daniele Campa; Elio Riboli; Tim Key; Henrik Gronberg; David J Hunter; Peter Kraft; Michael J Thun; Sue Ingles; Stephen Chanock; Demetrius Albanes; Richard B Hayes; David E Neal; Freddie C Hamdy; Jenny L Donovan; Paul Pharoah; Fredrick Schumacher; Brian E Henderson; Janet L Stanford; Elaine A Ostrander; Karina Dalsgaard Sorensen; Thilo Dörk; Gerald Andriole; Joanne L Dickinson; Cezary Cybulski; Jan Lubinski; Amanda Spurdle; Judith A Clements; Suzanne Chambers; Joanne Aitken; R A Frank Gardiner; Stephen N Thibodeau; Dan Schaid; Esther M John; Christiane Maier; Walther Vogel; Kathleen A Cooney; Jong Y Park; Lisa Cannon-Albright; Hermann Brenner; Tomonori Habuchi; Hong-Wei Zhang; Yong-Jie Lu; Radka Kaneva; Ken Muir; Sara Benlloch; Daniel A Leongamornlert; Edward J Saunders; Malgorzata Tymrakiewicz; Nadiya Mahmud; Michelle Guy; Lynne T O'Brien; Rosemary A Wilkinson; Amanda L Hall; Emma J Sawyer; Tokhir Dadaev; Jonathan Morrison; David P Dearnaley; Alan Horwich; Robert A Huddart; Vincent S Khoo; Christopher C Parker; Nicholas Van As; Christopher J Woodhouse; Alan Thompson; Tim Christmas; Chris Ogden; Colin S Cooper; Aritaya Lophatonanon; Melissa C Southey; John L Hopper; Dallas R English; Tiina Wahlfors; Teuvo L J Tammela; Peter Klarskov; Børge G Nordestgaard; M Andreas Røder; Anne Tybjærg-Hansen; Stig E Bojesen; Ruth Travis; Federico Canzian; Rudolf Kaaks; Fredrik Wiklund; Markus Aly; Sara Lindstrom; W Ryan Diver; Susan Gapstur; Mariana C Stern; Roman Corral; Jarmo Virtamo; Angela Cox; Christopher A Haiman; Loic Le Marchand; Liesel Fitzgerald; Suzanne Kolb; Erika M Kwon; Danielle M Karyadi; Torben Falck Orntoft; Michael Borre; Andreas Meyer; Jürgen Serth; Meredith Yeager; Sonja I Berndt; James R Marthick; Briony Patterson; Dominika Wokolorczyk; Jyotsna Batra; Felicity Lose; Shannon K McDonnell; Amit D Joshi; Ahva Shahabi; Antje E Rinckleb; Ana Ray; Thomas A Sellers; Hui-Yi Lin; Robert A Stephenson; James Farnham; Heiko Muller; Dietrich Rothenbacher; Norihiko Tsuchiya; Shintaro Narita; Guang-Wen Cao; Chavdar Slavov; Vanio Mitev; Douglas F Easton; Rosalind A Eeles
Journal:  Nat Genet       Date:  2011-07-10       Impact factor: 38.330

3.  Carnosic acid modulates Akt/IKK/NF-κB signaling by PP2A and induces intrinsic and extrinsic pathway mediated apoptosis in human prostate carcinoma PC-3 cells.

Authors:  Susanta Kar; Shreyasi Palit; Writoban Basu Ball; Pijush K Das
Journal:  Apoptosis       Date:  2012-07       Impact factor: 4.677

4.  Confirmation of the HOXB13 G84E germline mutation in familial prostate cancer.

Authors:  Joan P Breyer; T Grant Avritt; Kate M McReynolds; William D Dupont; Jeffrey R Smith
Journal:  Cancer Epidemiol Biomarkers Prev       Date:  2012-06-19       Impact factor: 4.254

5.  Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up.

Authors:  Fritz H Schröder; Jonas Hugosson; Monique J Roobol; Teuvo L J Tammela; Marco Zappa; Vera Nelen; Maciej Kwiatkowski; Marcos Lujan; Liisa Määttänen; Hans Lilja; Louis J Denis; Franz Recker; Alvaro Paez; Chris H Bangma; Sigrid Carlsson; Donella Puliti; Arnauld Villers; Xavier Rebillard; Matti Hakama; Ulf-Hakan Stenman; Paula Kujala; Kimmo Taari; Gunnar Aus; Andreas Huber; Theo H van der Kwast; Ron H N van Schaik; Harry J de Koning; Sue M Moss; Anssi Auvinen
Journal:  Lancet       Date:  2014-08-06       Impact factor: 79.321

6.  The G84E mutation of HOXB13 is associated with increased risk for prostate cancer: results from the REDUCE trial.

Authors:  Zhuo Chen; Celia Greenwood; William B Isaacs; William D Foulkes; Jielin Sun; Sigun L Zheng; Lynn D Condreay; Jianfeng Xu
Journal:  Carcinogenesis       Date:  2013-02-07       Impact factor: 4.944

7.  Long noncoding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer.

Authors:  Shancheng Ren; Yawei Liu; Weidong Xu; Yi Sun; Ji Lu; Fubo Wang; Min Wei; Jian Shen; Jianguo Hou; Xu Gao; Chuanliang Xu; Jiaoti Huang; Yi Zhao; Yinghao Sun
Journal:  J Urol       Date:  2013-07-08       Impact factor: 7.450

8.  Prevalence of the HOXB13 G84E germline mutation in British men and correlation with prostate cancer risk, tumour characteristics and clinical outcomes.

Authors:  Z Kote-Jarai; C Mikropoulos; D A Leongamornlert; T Dadaev; M Tymrakiewicz; E J Saunders; M Jones; S Jugurnauth-Little; K Govindasami; M Guy; F C Hamdy; J L Donovan; D E Neal; J A Lane; D Dearnaley; R A Wilkinson; E J Sawyer; A Morgan; A C Antoniou; R A Eeles
Journal:  Ann Oncol       Date:  2015-01-16       Impact factor: 32.976

9.  HOXB13 overexpression is an independent predictor of early PSA recurrence in prostate cancer treated by radical prostatectomy.

Authors:  Cristina Villares Zabalza; Meike Adam; Christoph Burdelski; Waldemar Wilczak; Corina Wittmer; Stefan Kraft; Till Krech; Stefan Steurer; Christina Koop; Claudia Hube-Magg; Markus Graefen; Hans Heinzer; Sarah Minner; Ronald Simon; Guido Sauter; Thorsten Schlomm; Maria Christina Tsourlakis
Journal:  Oncotarget       Date:  2015-05-20

10.  Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.

Authors:  Rosalind A Eeles; Ali Amin Al Olama; Sara Benlloch; Edward J Saunders; Daniel A Leongamornlert; Malgorzata Tymrakiewicz; Maya Ghoussaini; Craig Luccarini; Joe Dennis; Sarah Jugurnauth-Little; Tokhir Dadaev; David E Neal; Freddie C Hamdy; Jenny L Donovan; Ken Muir; Graham G Giles; Gianluca Severi; Fredrik Wiklund; Henrik Gronberg; Christopher A Haiman; Fredrick Schumacher; Brian E Henderson; Loic Le Marchand; Sara Lindstrom; Peter Kraft; David J Hunter; Susan Gapstur; Stephen J Chanock; Sonja I Berndt; Demetrius Albanes; Gerald Andriole; Johanna Schleutker; Maren Weischer; Federico Canzian; Elio Riboli; Tim J Key; Ruth C Travis; Daniele Campa; Sue A Ingles; Esther M John; Richard B Hayes; Paul D P Pharoah; Nora Pashayan; Kay-Tee Khaw; Janet L Stanford; Elaine A Ostrander; Lisa B Signorello; Stephen N Thibodeau; Dan Schaid; Christiane Maier; Walther Vogel; Adam S Kibel; Cezary Cybulski; Jan Lubinski; Lisa Cannon-Albright; Hermann Brenner; Jong Y Park; Radka Kaneva; Jyotsna Batra; Amanda B Spurdle; Judith A Clements; Manuel R Teixeira; Ed Dicks; Andrew Lee; Alison M Dunning; Caroline Baynes; Don Conroy; Melanie J Maranian; Shahana Ahmed; Koveela Govindasami; Michelle Guy; Rosemary A Wilkinson; Emma J Sawyer; Angela Morgan; David P Dearnaley; Alan Horwich; Robert A Huddart; Vincent S Khoo; Christopher C Parker; Nicholas J Van As; Christopher J Woodhouse; Alan Thompson; Tim Dudderidge; Chris Ogden; Colin S Cooper; Artitaya Lophatananon; Angela Cox; Melissa C Southey; John L Hopper; Dallas R English; Markus Aly; Jan Adolfsson; Jiangfeng Xu; Siqun L Zheng; Meredith Yeager; Rudolf Kaaks; W Ryan Diver; Mia M Gaudet; Mariana C Stern; Roman Corral; Amit D Joshi; Ahva Shahabi; Tiina Wahlfors; Teuvo L J Tammela; Anssi Auvinen; Jarmo Virtamo; Peter Klarskov; Børge G Nordestgaard; M Andreas Røder; Sune F Nielsen; Stig E Bojesen; Afshan Siddiq; Liesel M Fitzgerald; Suzanne Kolb; Erika M Kwon; Danielle M Karyadi; William J Blot; Wei Zheng; Qiuyin Cai; Shannon K McDonnell; Antje E Rinckleb; Bettina Drake; Graham Colditz; Dominika Wokolorczyk; Robert A Stephenson; Craig Teerlink; Heiko Muller; Dietrich Rothenbacher; Thomas A Sellers; Hui-Yi Lin; Chavdar Slavov; Vanio Mitev; Felicity Lose; Srilakshmi Srinivasan; Sofia Maia; Paula Paulo; Ethan Lange; Kathleen A Cooney; Antonis C Antoniou; Daniel Vincent; François Bacot; Daniel C Tessier; Zsofia Kote-Jarai; Douglas F Easton
Journal:  Nat Genet       Date:  2013-04       Impact factor: 38.330
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  9 in total

1.  Prostate cancer risk variants of the HOXB genetic locus.

Authors:  William D Dupont; Joan P Breyer; Spenser H Johnson; W Dale Plummer; Jeffrey R Smith
Journal:  Sci Rep       Date:  2021-05-31       Impact factor: 4.996

2.  HOXB13 networking with ABCG1/EZH2/Slug mediates metastasis and confers resistance to cisplatin in lung adenocarcinoma patients.

Authors:  Jun Zhan; Peng Wang; Shuai Li; Jiagui Song; Huiying He; Yunling Wang; Zhaofei Liu; Fan Wang; Hua Bai; Weigang Fang; Quan Du; Min Ye; Zhijie Chang; Jie Wang; Hongquan Zhang
Journal:  Theranostics       Date:  2019-04-06       Impact factor: 11.556

3.  Prognostic Significance of CIP2A in Esophagogastric Junction Adenocarcinoma: A Study of 65 Patients and a Meta-Analysis.

Authors:  Yanhong Li; Mei Wang; Xueping Zhu; Xu Cao; Yi Wu; Fang Fang
Journal:  Dis Markers       Date:  2019-08-22       Impact factor: 3.434

Review 4.  Molecular implications of HOX genes targeting multiple signaling pathways in cancer.

Authors:  U Sangeetha Shenoy; Divya Adiga; Shama Prasada Kabekkodu; Keith D Hunter; Raghu Radhakrishnan
Journal:  Cell Biol Toxicol       Date:  2021-10-06       Impact factor: 6.691

5.  HOXB13 and TFF3 can contribute to the prognostic stratification of prostate adenocarcinoma.

Authors:  Andrei Daniel Timofte; Simona Eliza Giuşcă; Ludmila Lozneanu; Mariana Bianca Manole; Iulian Prutianu; Bogdan Gafton; Andreea Rusu; Irina Draga Căruntu
Journal:  Rom J Morphol Embryol       Date:  2021 Jan-Mar       Impact factor: 1.033

6.  Novel prostate cancer susceptibility gene SP6 predisposes patients to aggressive disease.

Authors:  Csilla Sipeky; Teuvo L J Tammela; Anssi Auvinen; Johanna Schleutker
Journal:  Prostate Cancer Prostatic Dis       Date:  2021-05-19       Impact factor: 5.455

7.  Repurposing Multiple-Molecule Drugs for COVID-19-Associated Acute Respiratory Distress Syndrome and Non-Viral Acute Respiratory Distress Syndrome via a Systems Biology Approach and a DNN-DTI Model Based on Five Drug Design Specifications.

Authors:  Ching-Tse Ting; Bor-Sen Chen
Journal:  Int J Mol Sci       Date:  2022-03-26       Impact factor: 5.923

Review 8.  Downstream of the HOX genes: Explaining conflicting tumour suppressor and oncogenic functions in cancer.

Authors:  Richard Morgan; Keith Hunter; Hardev S Pandha
Journal:  Int J Cancer       Date:  2022-02-15       Impact factor: 7.316

9.  Cancerous Inhibitor of Protein Phosphatase 2A as a Molecular Marker for Aggressiveness and Survival in Oral Squamous Cell Carcinoma.

Authors:  Rajab Alzahrani; Amani A Alrehaili; Amal F Gharib; Farah Anjum; Khadiga A Ismail; Wael H Elsawy
Journal:  J Cancer Prev       Date:  2020-03-30
  9 in total

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