Ondrej Slaby George A Calin Editors Non coding RNAs in

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Advances in Experimental Medicine,and Biology,Volume 937. Editorial Board, IRUN R COHEN The Weizmann Institute of Science Rehovot Israel. N S ABEL LAJTHA Kline Institute for Psychiatric Research Orangeburg. JOHN D LAMBRIS University of Pennsylvania Philadelphia PA USA. RODOLFO PAOLETTI University of Milan Milan Italy, More information about this series at http www springer com series 5584. Ondrej Slaby George A Calin,Non coding RNAs,in Colorectal Cancer. Ondrej Slaby George A Calin, Central European Institute Department of Experimental.
Therapeutics Division of Cancer,of Technology Medicine. Masaryk University,The University of Texas MD Anderson. Brno Czech Republic,Cancer Center,Houston TX USA,ISSN 0065 2598 ISSN 2214 8019 electronic. Advances in Experimental Medicine and Biology, ISBN 978 3 319 42057 8 ISBN 978 3 319 42059 2 eBook. DOI 10 1007 978 3 319 42059 2,Library of Congress Control Number 2016949077.
Springer International Publishing Switzerland 2016. This work is subject to copyright All rights are reserved by the Publisher whether the whole or. part of the material is concerned specifically the rights of translation reprinting reuse of. illustrations recitation broadcasting reproduction on microfilms or in any other physical way. and transmission or information storage and retrieval electronic adaptation computer software. or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names registered names trademarks service marks etc in this. publication does not imply even in the absence of a specific statement that such names are. exempt from the relevant protective laws and regulations and therefore free for general use. The publisher the authors and the editors are safe to assume that the advice and information in. this book are believed to be true and accurate at the date of publication Neither the publisher nor. the authors or the editors give a warranty express or implied with respect to the material. contained herein or for any errors or omissions that may have been made. Printed on acid free paper, This Springer imprint is published by Springer Nature. The registered company is Springer International Publishing AG Switzerland. It was assumed that humans being highly complex organisms would have. many more genes than less complex organisms However the completion of. the Human Genome Project estimated the number of human genes to be. between 20 000 and 25 000 which is similar to genome of Caenorhabditis. elegans roundworm estimated to have around 20 000 genes and the num. ber of mice genes This revelation meant that organism complexity could not. be mainly the result of a higher number of protein coding genes Although. there was no correlation between complexity and the number of genes there. was a clear correlation with the relative amount of noncoding sequences in. the genome In humans only around 3 of the genome is protein coding. while the rest consists of introns regulatory sequences and noncoding. RNA These days 13 years after the completion of the Human Genome. Project research has rapidly progressed and we are now beginning to under. stand the importance of noncoding sequences in cellular regulatory processes. In cancer noncoding RNAs function as regulatory molecules acting as onco. genes and tumor suppressors with very important roles in cancer biology. This edited volume reflects the current state of knowledge about the roles. of noncoding RNAs in the formation and progression of colorectal cancer and. the potential translation of this knowledge to diagnosis and therapy of the. disease The main focus lies on involvement of noncoding RNAs in molecu. lar pathology of colorectal cancer together with cutting edge translational. research performed to transfer noncoding RNAs from bench to the bedside. We are sure that the emergence of noncoding RNAs represents a new dimen. sion of colorectal cancer pathogenesis and it will be absolutely necessary to. consider that in future translational studies This book will be a state of the. art resource for scientists or physicians starting out with noncoding RNA. research in colorectal cancer but is also intended for the experienced research. ers who want to incorporate noncoding RNA concepts into their colorectal. cancer research,Brno Czech Republic Ondrej Slaby,Houston TX USA George A Calin. Part I Non coding RNAs Biology and Implications,in Colorectal Cancer Pathogenesis. 1 Non coding RNAs Classification Biology,and Functioning 3. Sonja Hombach and Markus Kretz,2 Involvement of Non coding RNAs in the Signaling.
Pathways of Colorectal Cancer 19, Yinxue Yang Yong Du Xiaoming Liu and William C Cho. 3 MicroRNAs and Inflammation in Colorectal Cancer 53. Claire Josse and Vincent Bours,4 Interplay Between Transcription Factors. and MicroRNAs Regulating Epithelial Mesenchymal,Transitions in Colorectal Cancer 71. Markus Kaller and Heiko Hermeking,5 Non coding RNAs Functioning in Colorectal. Cancer Stem Cells 93,Daniele Fanale Nadia Barraco Angela List.
Viviana Bazan and Antonio Russo,6 MicroRNA Methylation in Colorectal Cancer 109. Sippy Kaur Johanna E Lotsari Salomaa,Riitta Sepp nen Kaijansinkko and P ivi Peltom ki. 7 Polymorphisms in Non coding RNA Genes,and Their Targets Sites as Risk Factors. of Sporadic Colorectal Cancer 123, Pavel Vodicka Barbara Pardini Veronika Vymetalkova. and Alessio Naccarati,Part II Non coding RNAs New Class of Biomarkers.
in Colorectal Cancer,8 Non coding RNAs as Biomarkers for Colorectal. Cancer Screening and Early Detection 153,Ondrej Slaby. viii Contents,9 Circulating Non coding RNA as Biomarkers. in Colorectal Cancer 171, Manuela Ferracin Laura Lupini Alessandra Mangolini. and Massimo Negrini, 10 Non coding RNAs Enabling Prognostic Stratification.
and Prediction of Therapeutic Response,in Colorectal Cancer Patients 183. Samantha O Perakis Joseph E Thomas and Martin Pichler. Part III Non coding RNAs Therapeutic Targets,and Colorectal Cancer Therapeutics. 11 Involvement of Non coding RNAs in Chemo,and Radioresistance of Colorectal Cancer 207. Daniele Fanale Marta Castiglia Viviana Bazan,and Antonio Russo. 12 Non coding RNAs Therapeutic Strategies,and Delivery Systems 229.
13 MicroRNAs as Therapeutic Targets and Colorectal. Cancer Therapeutics 239,Hirofumi Yamamoto and Masaki Mori. Non coding RNAs Biology and,Implications in Colorectal Cancer. Pathogenesis,Non coding RNAs Classi cation,Biology and Functioning 1. Sonja Hombach and Markus Kretz, One of the long standing principles of molecular biology is that DNA acts. as a template for transcription of messenger RNAs which serve as blue. prints for protein translation A rapidly growing number of exceptions to. this rule have been reported over the past decades they include long. known classes of RNAs involved in translation such as transfer RNAs and. ribosomal RNAs small nuclear RNAs involved in splicing events and. small nucleolar RNAs mainly involved in the modi cation of other small. RNAs such as ribosomal RNAs and transfer RNAs More recently several. classes of short regulatory non coding RNAs including piwi associated. RNAs endogenous short interfering RNAs and microRNAs have been. discovered in mammals which act as key regulators of gene expression in. many different cellular pathways and systems Additionally the human. genome encodes several thousand long non protein coding RNAs 200. nucleotides in length some of which play crucial roles in a variety of bio. logical processes such as epigenetic control of chromatin promoter spe. ci c gene regulation mRNA stability X chromosome inactivation and. imprinting In this chapter we will introduce several classes of short and. long non coding RNAs describe their diverse roles in mammalian gene. regulation and give examples for known modes of action. Non coding RNA miRNA piRNA snoRNA snRNA tRNA rRNA,lncRNA Classi cation Biogenesis Function.
1 1 Introduction,S Hombach M Kretz, Institute of Biochemistry Genetics and Microbiology Gene expression is a central process required for. University of Regensburg Regensburg Germany all aspects of life and its regulation de nes. e mail sonja hombach ur de development and homeostasis of all cells and. markus kretz vkl uni regensburg de, Springer International Publishing Switzerland 2016 3. O Slaby G A Calin eds Non coding RNAs in Colorectal Cancer Advances in Experimental. Medicine and Biology 937 DOI 10 1007 978 3 319 42059 2 1. 4 S Hombach and M Kretz, tissues A central component of this process is the approximately 1 9 encodes for proteins 13. genomic DNA localized in the cell nucleus serv 15 A signi cant portion of this transcriptional. ing as a template for the transcription of activity appears to be represented by another. messenger RNAs which in turn translocate into class of regulatory ncRNAs the long non coding. the cytoplasm and act as blueprints for the trans RNAs lncRNAs These RNA molecules are. lation of proteins Several classes of non protein characterized by a length of at least 200 nucleo. coding RNAs ncRNAs are needed for these tides a lack of protein coding potential and often. processes to function Small nuclear RNAs harbor a poly A tail and can be spliced similar to. snRNAs are mainly involved in splicing events mRNAs While an estimated abundance of 5400. of mRNAs Transfer RNAs tRNAs decode the to more than 10 000 lncRNA transcripts has been. mRNA sequence into peptide or protein by spe reported in humans 15 17 exact genomic. ci cally recognizing three nucleotide sequences annotations and functional signi cance are still. of mRNAs and recruiting amino acids to the ribo unknown for many lncRNAs to date Nevertheless. some in the right order Ribosomal RNAs a rapidly growing number of lncRNAs have been. rRNAs are thought to represent the most abun shown to play crucial roles in a variety of biologi. dant RNA molecules in the cell and form the cal processes such as epigenetic control of gene. framework of ribosomes macromolecular struc expression promoter speci c gene regulation. tures essential for protein translation These 18 20 X chromosome inactivation 21 23. housekeeping RNAs are constitutively expressed imprinting 24 28 maintenance of nuclear. and essential for normal function of the cell A architecture 29 31. signi cant portion of these housekeeping RNAs Both small and long regulatory non coding. may carry chemical modi cations which are RNAs have been implicated in many different dis. added by a class of small nucleolar RNAs eases and many types of cancer 32 34 In the. snoRNAs 1 following paragraphs several functional charac. The discovery of small regulatory ncRNAs in teristics of short and long ncRNAs will be eluci. the 1990s completely changed our understanding dated and examples for known modes of actions. of ncRNAs as regulatory molecules Andrew in gene regulatory processes will be discussed. Fire Craig Mello et al could show that small,double stranded RNAs dsRNAs were able to. mediate post transcriptional gene silencing of 1 2 Characteristics and Modes. complementary mRNAs in the nematode of Action of Short. Caenorhabditis elegans by a process called RNA Regulatory. interference 2 3 Quickly endogenous dsRNAs Non coding RNAs. such as small interfering RNAs siRNAs and, microRNAs miRNAs were found in a multi Small ncRNAs have emerged as key regulators.
tude of organisms such as plants ies and mam of gene expression in many different cellular. mals A growing number of new regulatory small pathways and systems A multitude of small reg. RNA classes has been discovered in recent years ulatory RNA classes have been identi ed in. 4 with piwi associated RNAs miRNAs and recent years with miRNAs piRNAs and siRNAs. siRNAs belonging to the best investigated classes being the most thoroughly investigated classes. to date 5 12,With the rapidly increasing development of. high throughput in depth transcriptome sequenc 1 2 1 MicroRNAs. ing techniques our understanding of the protein, coding and non coding portion of the mammalian MiRNAs directly interact with partially comple. transcriptome increased exponentially Recent mentary target sites located in the 3 untranslated. studies suggest that while about two thirds of the region of target mRNAs and repress their expres. mammalian genome is actively transcribed only sion 35 They play essential roles during differ. 1 Non coding RNAs Classification Biology and Functioning 5. entiation and development More than 60 of all encoded by a gene cluster such as the miR. mRNAs are estimated to contain miRNA target 17 92 gene cluster A recent study showed that. sites at their 3 UTR region suggesting a tight processing of the pri miR 17 92a transcript. regulation as well as their involvement in normal containing all six miRNAs from this cluster. cellular homeostasis and in diseased states 36 includes formation of a processing intermediate. In addition it has been shown that many miRNAs called progenitor miRNA pro miRNA 44. are able to target up to several hundred mRNAs While the pro miRNA is ef ciently processed by. suggesting a complex and combinatorial mode of the microprocessor complex Fig 1 1 the pri. miRNA action in mRNA regulation 37 In miR 17 92a on the other hand can adopt an. recent years a growing number of studies could RNA confor. O Slaby G A Calin eds Non coding RNAs in Colorectal Cancer Advances in Experimental Medicine and Biology 937 DOI 10 1007 978 3 319 42059 2 1 Non coding RNAs Classi cation Biology and unctioning F Sonja Hombach and Markus Kretz Abstract

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