Hui Ling1, Karen Pickard2, Cristina Ivan3, Alex Mirnezami2,4, George A Calin1,3, Milena S Nicoloso1,5, Claudio Isella6,7, Mariko Ikuo1,8, Richard Mitter9, Riccardo Spizzo1,5, Marc Bullock1,2, Cornelia Braicu10, Valentina Pileczki10, Kimberly Vincent1, Martin Pichler1,11, Verena Stiegelbauer11, Gerald Hoefler12, Maria I Almeida1,13, Annie Hsiao1, Xinna Zhang3, John Primrose2,4, Graham Packham2, Kevin Liu1, Krishna Bojja1, Roberta Gafà14, Lianchun Xiao15, Simona Rossi1, Jian H Song16, Ivan Vannini17, Francesca Fanini17, Scott Kopetz18, Patrick Zweidler-McKay19, Xuemei Wang15, Calin Ionescu20,21, Alexandru Irimie22, Muller Fabbri23,17, Giovanni Lanza14, Stanley R Hamilton24, Ioana Berindan-Neagoe10,25, Enzo Medico6,7. 1. Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 2. Cancer Research UK Centre, University of Southampton Cancer Sciences Division, Somers Cancer Research Building, Southampton University Hospital NHS Trust, Tremona road, Southampton, SO16 6YD, UK. 3. Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 4. Department of Surgery, Southampton University Hospital NHS Trust, Tremona road, Southampton, SO16 6YD, UK. 5. Division of Experimental Oncology B, CRO, National Cancer Institute, Aviano, Italy. 6. University of Torino, Department of Oncology, Torino, Italy. 7. IRCC, Institute for Cancer Research and Treatment, Candiolo, Torino, Italy. 8. Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan. 9. Bioinformatics Unit, London Research Institute, Cancer Research UK, London, UK. 10. Department of Functional Genomics, The Oncology Institute, Cluj-Napoca, Romania. 11. Division of Oncology, Medical University of Graz, Austria. 12. Institute of Pathology, Medical University of Graz, Austria. 13. INEB, Instituto de Engenharia Biomedica, University of Porto, Porto, Portugal. 14. Section of Pathology and Molecular Diagnostics, University of Ferrara, Ferrara, Italy. 15. Division of Quantitative Science, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. 16. Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 17. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) s.r.l., IRCCS, Gene Therapy Unit, Meldola (FC), Italy. 18. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 19. Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 20. Surgical Clinic 1, Cluj County Hospital, Romania. 21. UMF Surgery Department 1, Cluj-Napoca, Romania. 22. Department of Surgical and Gynecology Oncology, University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania. 23. Departments of Pediatrics, and Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, The Saban Research Institute, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, CA, USA. 24. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 25. Research Center for Functional Genomics, Biomedicine and Translational Medicine, University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania.
Abstract
OBJECTIVE: MicroRNA (miRNA) expression profile can be used as prognostic marker for human cancers. We aim to explore the significance of miRNAs in colorectal cancer (CRC) metastasis. DESIGN: We performed miRNA microarrays using primary CRC tissues from patients with and without metastasis, and validated selected candidates in 85 CRC samples by quantitative real-time PCR (qRT-PCR). We tested metastatic activity of selected miRNAs and identified miRNA targets by prediction algorithms, qRT-PCR, western blot and luciferase assays. Clinical outcomes were analysed in six sets of CRC cases (n=449), including The Cancer Genome Atlas (TCGA) consortium and correlated with miR-224 status. We used the Kaplan-Meier method and log-rank test to assess the difference in survival between patients with low or high levels of miR-224 expression. RESULTS: MiR-224 expression increases consistently with tumour burden and microsatellite stable status, and miR-224 enhances CRC metastasis in vitro and in vivo. We identified SMAD4 as a miR-224 target and observed negative correlation (Spearman Rs=-0.44, p<0.0001) between SMAD4 and miR-224 expression in clinical samples. Patients with high miR-224 levels display shorter overall survival in multiple CRC cohorts (p=0.0259, 0.0137, 0.0207, 0.0181, 0.0331 and 0.0037, respectively), and shorter metastasis-free survival (HR 6.51, 95% CI 1.97 to 21.51, p=0.0008). In the TCGA set, combined analysis of miR-224 with SMAD4 expression enhanced correlation with survival (HR 4.12, 95% CI 1.1 to 15.41, p=0.0175). CONCLUSIONS: MiR-224 promotes CRC metastasis, at least in part, through the regulation of SMAD4. MiR-224 expression in primary CRC, alone or combined with its targets, may have prognostic value for survival of patients with CRC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
OBJECTIVE: MicroRNA (miRNA) expression profile can be used as prognostic marker for humancancers. We aim to explore the significance of miRNAs in colorectal cancer (CRC) metastasis. DESIGN: We performed miRNA microarrays using primary CRC tissues from patients with and without metastasis, and validated selected candidates in 85 CRC samples by quantitative real-time PCR (qRT-PCR). We tested metastatic activity of selected miRNAs and identified miRNA targets by prediction algorithms, qRT-PCR, western blot and luciferase assays. Clinical outcomes were analysed in six sets of CRC cases (n=449), including The Cancer Genome Atlas (TCGA) consortium and correlated with miR-224 status. We used the Kaplan-Meier method and log-rank test to assess the difference in survival between patients with low or high levels of miR-224 expression. RESULTS:MiR-224 expression increases consistently with tumour burden and microsatellite stable status, and miR-224 enhances CRC metastasis in vitro and in vivo. We identified SMAD4 as a miR-224 target and observed negative correlation (Spearman Rs=-0.44, p<0.0001) between SMAD4 and miR-224 expression in clinical samples. Patients with high miR-224 levels display shorter overall survival in multiple CRC cohorts (p=0.0259, 0.0137, 0.0207, 0.0181, 0.0331 and 0.0037, respectively), and shorter metastasis-free survival (HR 6.51, 95% CI 1.97 to 21.51, p=0.0008). In the TCGA set, combined analysis of miR-224 with SMAD4 expression enhanced correlation with survival (HR 4.12, 95% CI 1.1 to 15.41, p=0.0175). CONCLUSIONS:MiR-224 promotes CRC metastasis, at least in part, through the regulation of SMAD4. MiR-224 expression in primary CRC, alone or combined with its targets, may have prognostic value for survival of patients with CRC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Authors: Panagiotis G Adamopoulos; Christos K Kontos; Stamatia-Maria Rapti; Iordanis N Papadopoulos; Andreas Scorilas Journal: Int J Oncol Date: 2014-11-24 Impact factor: 5.650
Authors: Zsuzsanna Lichner; Salvador Mejia-Guerrero; Monika Ignacak; Adriana Krizova; Tian Tian Bao; Andrew H F Girgis; Yousef M Youssef; George M Yousef Journal: Am J Pathol Date: 2012-02-09 Impact factor: 4.307
Authors: C R Boland; S N Thibodeau; S R Hamilton; D Sidransky; J R Eshleman; R W Burt; S J Meltzer; M A Rodriguez-Bigas; R Fodde; G N Ranzani; S Srivastava Journal: Cancer Res Date: 1998-11-15 Impact factor: 12.701
Authors: Harry L A Janssen; Hendrik W Reesink; Eric J Lawitz; Stefan Zeuzem; Maribel Rodriguez-Torres; Keyur Patel; Adriaan J van der Meer; Amy K Patick; Alice Chen; Yi Zhou; Robert Persson; Barney D King; Sakari Kauppinen; Arthur A Levin; Michael R Hodges Journal: N Engl J Med Date: 2013-03-27 Impact factor: 91.245
Authors: Arnaud D Roth; Mauro Delorenzi; Sabine Tejpar; Pu Yan; Dirk Klingbiel; Roberto Fiocca; Giovanni d'Ario; Laura Cisar; Roberto Labianca; David Cunningham; Bernard Nordlinger; Fred Bosman; Eric Van Cutsem Journal: J Natl Cancer Inst Date: 2012-10-25 Impact factor: 13.506
Authors: Junius Salendo; Melanie Spitzner; Frank Kramer; Xin Zhang; Peter Jo; Hendrik A Wolff; Julia Kitz; Silke Kaulfuß; Tim Beißbarth; Matthias Dobbelstein; Michael Ghadimi; Marian Grade; Jochen Gaedcke Journal: Radiother Oncol Date: 2013-08-07 Impact factor: 6.280
Authors: Martin Pichler; Cristian Rodriguez-Aguayo; Su Youn Nam; Mihnea Paul Dragomir; Recep Bayraktar; Simone Anfossi; Erik Knutsen; Cristina Ivan; Enrique Fuentes-Mattei; Sang Kil Lee; Hui Ling; Tina Catela Ivkovic; Guoliang Huang; Li Huang; Yoshinaga Okugawa; Hiroyuki Katayama; Ayumu Taguchi; Emine Bayraktar; Rajat Bhattacharya; Paola Amero; William Ruixian He; Anh M Tran; Petra Vychytilova-Faltejskova; Christiane Klec; Diana L Bonilla; Xinna Zhang; Sanja Kapitanovic; Bozo Loncar; Roberta Gafà; Zhihui Wang; Vittorio Cristini; Samir M Hanash; Menashe Bar-Eli; Giovanni Lanza; Ondrej Slaby; Ajay Goel; Isidore Rigoutsos; Gabriel Lopez-Berestein; George Adrian Calin Journal: Gut Date: 2020-01-27 Impact factor: 23.059
Authors: Martin Pichler; Verena Stiegelbauer; Petra Vychytilova-Faltejskova; Cristina Ivan; Hui Ling; Elke Winter; Xinna Zhang; Matthew Goblirsch; Annika Wulf-Goldenberg; Masahisa Ohtsuka; Johannes Haybaeck; Marek Svoboda; Yoshinaga Okugawa; Armin Gerger; Gerald Hoefler; Ajay Goel; Ondrej Slaby; George Adrian Calin Journal: Clin Cancer Res Date: 2016-09-06 Impact factor: 12.531
Authors: María Antonia Lizarbe; Jorge Calle-Espinosa; Eva Fernández-Lizarbe; Sara Fernández-Lizarbe; Miguel Ángel Robles; Nieves Olmo; Javier Turnay Journal: Biomed Res Int Date: 2017-05-10 Impact factor: 3.411
Authors: María Teresa Corcuera; Cruz Rodríguez-Bobada; Jaime Zuloaga; Fernando Gómez-Aguado; Rosa Rodríguez-Perez; Ángel Mendizabal; Pablo González; Javier Arias-Díaz; María Luisa Caballero Journal: Parasitol Res Date: 2018-07-13 Impact factor: 2.289
Authors: Jenny L Smith; Rhonda E Ries; Tiffany Hylkema; Todd A Alonzo; Robert B Gerbing; Marianne T Santaguida; Lisa Eidenschink Brodersen; Laura Pardo; Carrie L Cummings; Keith R Loeb; Quy Le; Suzan Imren; Amanda R Leonti; Alan S Gamis; Richard Aplenc; E Anders Kolb; Jason E Farrar; Timothy J Triche; Cu Nguyen; Daoud Meerzaman; Michael R Loken; Vivian G Oehler; Hamid Bolouri; Soheil Meshinchi Journal: Clin Cancer Res Date: 2019-11-12 Impact factor: 12.531