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This cancers from bench to bedside applications and are written bys an international team of renowned experts in the field. This booka ins ian tlearnndamtioanrka l wteoarmk porfo rveindoinwgn eudp -etoxp-dearttes irne stehaer cfhie lodn. This is book is a landmark work providing up-to-date research on in miRNAs and their important roles in cancer translational book is a landmark work providing up-to-date research onn i miRNAs and their important roles in cancer translational research. n miRNAs and their important roles in cancer translational C research. C research. aC a na n cn c e c e re r r C CLé Léas C auresar urenar LLauésa K16750 nce A. MarchatLópez-Camarilloce A. MarchatEditorsópez-Camarillorence A. MarchaEditorsr López-Camaril Editors CésCaLéras CLuaéórrEs epLadneóriczEt po-eLdCer óAiszEatpo-.mdC erMiszaato-mraCrirslaaclmrohialaltroillo tlo Laurence A. Marchat Laurence A. Marchat 6000 Broken Sound Parkway, NW Suite 300, Boca Raton, FL 33487 711 Third Avenue New York, NY 10017 an informa business 2 Park Square, Milton Park www.taylorandfrancisgroup.com Abingdon, Oxon OX14 4RN, UK A ScieNce PUBLiSheRS BOOK MicroRNAs in Cancer TThhiiss ppaaggee iinntteennttiioonnaallllyy lleefftt bbllaannkk MicroRNAs in Cancer Editors César López-Camarillo Oncogenomics and Cancer Proteomics Laboratory Autonomous University of Mexico City Mexico City México Laurence A. Marchat Multidisciplinary Program in Biomedicine National School of Medicine and Homeopathy-IPN Mexico City Mexico p, A SCIENCE PUBLISHERS BOOK GL--Prelims with new title page.indd ii 4/25/2012 9:52:40 AM CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2013 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Version Date: 20130325 International Standard Book Number-13: 978-1-4665-7677-3 (eBook - PDF) This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information stor- age or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copy- right.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that pro- vides licenses and registration for a variety of users. For organizations that have been granted a pho- tocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com PREFACE Cancer is a complex group of diseases characterized by the presence of cells with uncontrolled growth and high proliferation capability. It is the leading cause of death in most countries, affecting millions of people worldwide and representing a global health problem. Cancer has huge economic, social and psychological implications. Even till now cancer remains a major clinical challenge due to its frequently poor prognosis and limited treatment options in many cases. Thus there is an urgent need for the development of new molecular methods that will allow an early diagnosis and better treatment. The recent development of “omics” technologies, such as proteomics and transcriptomics has opened new research areas for scientists working in cancer. Notably, the discovery of the relevance of microRNAs in the mechanisms leading to tumorigenesis has allowed a better understanding of the molecular events involved in carcinogenesis. MicroRNAs are a class of small non-coding single-stranded RNAs that play important roles in most biological processes by regulating gene expression through transcriptional repression and degradation of protein-coding messenger RNAs. MicroRNA biology is a cutting-edge topic in the basic and biomedical research fi elds. Dysregulation of microRNA expression levels emerges as an important mechanism that triggers the loss or gain of functions in cancer cells, acting as tumor suppressors and oncogenes. This book is an invaluable collection of the recent fi ndings and reviews of leading experts about the current understanding of roles of microRNAs in the development, progression, invasion and metastasis of the most common cancers. It also reviews their potential for applications as novel molecular markers for early diagnosis and prognosis, as well as for the identifi cation of therapeutic targets. In addition, it provides discussions about their potential use in translational medicine. Topics include an integrated overview of microRNAs functions in a variety of neoplasias including breast, prostate, colorectal, cervix, gastric and lung cancer as well as melanoma, and medulloblastoma. In addition, this volume includes a comprehensive coverage of key high-throughput technologies that have vi MicroRNAs in Cancer been developed for clinically oriented microRNAs profi ling. Perspectives of quantitative sciences including bioinformatics, system biology and mathematical modeling are also discussed. This book constitutes an essential reference for the graduates students, post-docs, researchers and for scientifi c and medical community by providing the up-to-date discoveries of an international team of renowned experts in the fi eld about microRNAs and their important roles in cancer translational research. CONTENTS Preface v 1. Breast Cancer MicroRNAs: Signaling Networks and Clinical 1 Applications Gabriel Eades, Yuan Yao and Qun Zhou 2. MicroRNAs in Breast Cancer Development 44 Mei Yang, Zhe Xu, Yuxin Zhang and Chenfang Zhang 3. MicroRNAs Controlling Invasion and Metastasis in 64 Breast Cancer César López-Camarillo, Laurence A. Marchat and José Ali Flores-Perez 4. Endometrial Cancer and MicroRNAs 80 Jaime Snowdon and Harriet Feilotter 5. MicroRNAs in Cervical Cancer: Evidences of a miRNA 105 De-regulation Caused by HPV Carlos Pérez-Plasencia, Nadia Jacobo-Herrera, Carlos Barba-Ostria, Rosa Alvarez-Gómez, David Cantú-De León, Jorge Fernández-Retana, Elena Arechaga-Ocampo, Luis A. Herrera, César López-Camarillo and Oscar Peralta-Zaragoza 6. MicroRNAs in Prostate Cancer 128 Aya Misawa, Ken-ichi Takayama and Satoshi Inoue 7. MicroRNA Deregulations in Gastric Cancer 156 Jiayi Yao, Tusheng Song and Chen Huang 8. MicroRNAs in Colorectal Cancer 177 K. Valencia, E. Bandres and J. Garcia-Foncillas viii MicroRNAs in Cancer 9. MicroRNAs in Lung Cancer: From Genomics to Clinical 220 Applications Elena Arechaga-Ocampo, Jose Diaz-Chavez, Cesar Lopez- Camarillo, Eduardo Lopez-Urrutia, Claudia H. Gonzalez de la Rosa, Carlos Perez-Plasencia, Yamilet Noriega Reyes and Luis A. Herrera 10. MicroRNAs in Melanoma 252 Federica Felicetti, Maria Cristina Errico, Gianfranco Mattia, Nadia Felli and Alessandra Carè 11. MicroRNAs in Medulloblastoma 278 Tarek Shalaby, Martin Baumgartner, Giulio Fiaschetti and Michael A. Grotzer 12. Extracellular MicroRNAs as Potential Biomarkers and 308 Therapeutic Tools in Cancer Muriel Thirion and Takahiro Ochiya 13. MicroRNAs as Potential Therapeutic Targets in Cancer 333 Ailbhe M. McDermott, Helen M. Heneghan, Nicola Miller and Michael J. Kerin 14. Regulation of MicroRNAs for Potential Cancer 364 Therapeutics: The Paradigm Shift from Pathways to Perturbation of Gene Regulatory Networks Wei Wu, Wei Cao and Jennifer A. Chan 15. Systems and Network Biology in MicroRNA based 387 Personalized Medicine Asfar S. Azmi, Bin Bao, Philip A. Philip, Ramzi M. Mohammad and Fazlul H. Sarkar Index 405 Color Plate Section 407 CHAPTER 1 BREAST CANCER MicroRNAs: SIGNALING NETWORKS AND CLINICAL APPLICATIONS Gabriel Eades,a Yuan Yaob and Qun Zhouc,* ABSTRACT The abundant, non-coding regulatory molecules, microRNAs, are heavily implicated in the molecular pathobiology of breast cancer. In this review, we will discuss how microRNA networks contribute to key pathways and processes in breast cancer including hormone and growth factor signaling as well as drug resistance. We will also describe the connection between microRNAs, epigenetic pathways, and gene expression in breast cancer. Finally, we will explore recent work evaluating microRNAs as clinical tools and will discuss the potential for microRNAs to serve as prognostic biomarkers and therapeutic targets in breast cancer. 1. INTRODUCTION Breast cancer is a heterogeneous disease consisting of several histological types and multiple molecular subtypes driven by genetic and epigenetic Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 N. Greene St. Baltimore, MD 21201, 410-706-1615. aEmail: [email protected] bEmail: [email protected] cEmail: [email protected] *Corresponding author