Polymorphisms within micro-RNA-binding sites and risk of sporadic colorectal cancer
Debora Landi,Federica Gemignani,Alessio Naccarati,Barbara Pardini,Pavel Vodicka,Ludmila Vodickova,Jan Novotny,Asta Försti,Asta Försti,Kari Hemminki,Federico Canzian,Stefano Landi +11 more
TLDR
This study selected the 3' UTRs of 104 genes candidate for colorectal cancer and identified putative miRNA-binding sites by specialized algorithms, finding statistically significant associations between risk of CRC and variant alleles of CD86 and INSR genes.Abstract:
Recent evidence indicate that small non-coding RNA molecules, called micro-RNAs (miRNAs), can bind to the 3' untranslated regions (UTRs) of messenger RNAs and interfere with their translation, thereby regulating cell growth, differentiation, apoptosis and tumorigenesis. Genetic polymorphisms can reside on miRNA-binding sites. Thus, it is conceivable that the miRNA regulation may be affected by polymorphisms on the 3' UTRs. Since gene deregulation is one of the key mechanisms by which cells can progress to cancer, we hypothesize that common polymorphisms within miRNA-target binding sites could play a role in the individual risk of cancer. In the present study, we selected the 3' UTRs of 104 genes candidate for colorectal cancer (CRC) and we identified putative miRNA-binding sites by specialized algorithms (PicTar, DianaMicroT, miRBase, miRanda, TargetScan and microInspector). Fifty-seven single-nucleotide polymorphisms (SNPs) were identified in miRNA-binding sites. We evaluated the SNPs for their ability to affect the binding of the miRNA with its target, by assessing the variation of Gibbs free energy between the two alleles of each SNP. We found eight common polymorphisms that were further investigated by a case-control association studies. The study was carried out on a series of cases and controls from Czech Republic, a population with the highest worldwide incidence of CRC. We found statistically significant associations between risk of CRC and variant alleles of CD86 [odds ratio (OR) = 2.74; 95% confidence interval (CI) = 1.24-6.04, for the variant homozygotes] and INSR genes (OR = 1.94; 95% CI = 1.03-3.66, for the variant homozygotes). These results are the first reporting positive association between miRNA-binding SNPs sequences and cancer risk.read more
Citations
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The MIQE Guidelines: Minimum Information for Publication of Quantitative Real-Time PCR Experiments
Stephen A. Bustin,Vladimir Benes,Jeremy A. Garson,Jan Hellemans,Jim F. Huggett,Mikael Kubista,Reinhold Mueller,Tania Nolan,Michael W. Pfaffl,Gregory L. Shipley,Jo Vandesompele,Carl T. Wittwer,Carl T. Wittwer +12 more
TL;DR: The Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines target the reliability of results to help ensure the integrity of the scientific literature, promote consistency between laboratories, and increase experimental transparency.
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Genetic variation in microRNA networks: the implications for cancer research
TL;DR: In reviewing this new field of cancer biology, the methodological approaches of these studies are described, and recommendations for which strategies will be most informative in the future are made.
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MicroRNA related polymorphisms and breast cancer risk
Sofia Khan,Dario Greco,Dario Greco,Kyriaki Michailidou,Roger L. Milne,Roger L. Milne,Taru A. Muranen,Tuomas Heikkinen,Kirsimari Aaltonen,Joe Dennis,Manjeet K. Bolla,Jianjun Liu,Per Hall,Astrid Irwanto,Keith Humphreys,Jingmei Li,Kamila Czene,Jenny Chang-Claude,Rebecca Hein,Anja Rudolph,Petra Seibold,Dieter Flesch-Janys,Olivia Fletcher,Julian Peto,Isabel dos Santos Silva,Nichola Johnson,Lorna Gibson,Zoe Aitken,John L. Hopper,Helen Tsimiklis,Minh Bui,Enes Makalic,Daniel F. Schmidt,Melissa C. Southey,Carmel Apicella,Jennifer Stone,Quinten Waisfisz,Hanne Meijers-Heijboer,Muriel A. Adank,Rob B. van der Luijt,Alfons Meindl,Rita K. Schmutzler,Bertram Müller-Myhsok,Peter Lichtner,Clare Turnbull,Nazneen Rahman,Stephen J. Chanock,David J. Hunter,Angela Cox,Simon S. Cross,Malcolm W.R. Reed,Marjanka K. Schmidt,Annegien Broeks,Laura Van't Veer,Frans B. L. Hogervorst,Peter A. Fasching,Michael G. Schrauder,Arif B. Ekici,Matthias W. Beckmann,Stig E. Bojesen,Børge G. Nordestgaard,Sune F. Nielsen,Henrik Flyger,Javier Benitez,Pilar Zamora,Jose Ignacio Arias Perez,Christopher A. Haiman,Brian E. Henderson,Fredrick R. Schumacher,Loic Le Marchand,Paul D.P. Pharoah,Alison M. Dunning,Mitul Shah,Robert Luben,Judith E. Brown,Fergus J. Couch,Xianshu Wang,Celine M. Vachon,Janet E. Olson,Diether Lambrechts,Matthieu Moisse,Robert Paridaens,Marie-Rose Christiaens,Pascal Guénel,Thérèse Truong,Pierre Laurent-Puig,Claire Mulot,F Marmé,Barbara Burwinkel,Andreas Schneeweiss,Christof Sohn,Elinor J. Sawyer,Ian Tomlinson,Michael J. Kerin,Nicola Miller,Irene L. Andrulis,Julia A. Knight,Sandrine Tchatchou,Anna Marie Mulligan,Thilo Dörk,Natalia Bogdanova,Natalia Antonenkova,Hoda Anton-Culver,Hatef Darabi,Mikael Eriksson,Montserrat Garcia-Closas,Jonine D. Figueroa,Jolanta Lissowska,Louise A. Brinton,Peter Devilee,Robert A.E.M. Tollenaar,Caroline Seynaeve,Christi J. van Asperen,Vessela N. Kristensen,Susan L. Slager,Amanda E. Toland,Christine B. Ambrosone,Drakoulis Yannoukakos,Annika Lindblom,Sara Margolin,Paolo Radice,Paolo Peterlongo,Monica Barile,Paolo Mariani,Maartje J. Hooning,John W.M. Martens,J. Margriet Collée,Agnes Jager,Anna Jakubowska,Jan Lubinski,Katarzyna Jaworska-Bieniek,Katarzyna Durda,Graham G. Giles,Catriona McLean,Hiltrud Brauch,Thomas Brüning,Yon-Dschun Ko,Hermann Brenner,Aida Karina Dieffenbach,Volker Arndt,Christa Stegmaier,Anthony J. Swerdlow,Alan Ashworth,Nick Orr,Michael Jones,Jacques Simard,Mark S. Goldberg,Martine Dumont,Robert Winqvist,Katri Pylkäs,Arja Jukkola-Vuorinen,Mervi Grip,Vesa Kataja,Veli-Matti Kosma,Jaana M. Hartikainen,Arto Mannermaa,Ute Hamann,Georgia Chenevix-Trench,Carl Blomqvist,Kristiina Aittomäki,Douglas F. Easton,Heli Nevanlinna +161 more
TL;DR: Five miRNA binding site SNPs associated significantly with breast cancer risk are located in the 3′ UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively, which belongs to miRNA machinery genes and has a central role in initial miRNA processing.
Journal ArticleDOI
Inflammation and cancer: interweaving microRNA, free radical, cytokine and p53 pathways
TL;DR: A general overview of the connection between inflammation, microRNAs and cancer is provided and how improved understanding of these connections may provide novel preventive, diagnostic and therapeutic strategies to reduce the health burden of cancer is highlighted.
Journal ArticleDOI
MicroRNAs in colorectal cancer: translation of molecular biology into clinical application
TL;DR: The knowledge regarding miRNAs' functioning in CRC is summarized while emphasizing their significance in pathogenetic signaling pathways and their potential to serve as disease biomarkers and novel therapeutic targets.
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