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Polymorphisms affecting micro-RNA regulation and associated with the risk of dietary-related cancers: A review from the literature and new evidence for a functional role of rs17281995 (CD86) and rs1051690 (INSR), previously associated with colorectal cancer.
MedLine Citation:
PMID:  20971123     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
In this review, we focus on the genetic variations (single nucleotide polymorphisms, SNPs) known to occur in microRNAs and in their binding sites and the susceptibility to cancers of the gastro-intestinal (GI) tract in humans. Since the sequence complementarity and the thermodynamics of binding play an essential role in the interaction of miRNA with its target mRNA, sequence variations in the miRNA-binding seed regions or in miRNA genes (either within pre-, pri-, or mature miRNA regions) should reinforce, weaken, or disrupt the miRNA-mRNA interaction and affect the expression of mRNA targets. Indirect evidences supporting these hypotheses are reported in the literature, essentially coming from case-control association studies. Several studies have been published on the association between miR-SNPs or SNPs within their binding sites and the risk of oesophageal, gastric, or colorectal cancer. Unfortunately, functional studies are lacking. Besides reviewing the available literature, we present here for the first time two SNPs (rs17281995 in CD86 and rs1051690 in INSR) previously associated with the risk of CRC in a Czech population are also associated with the risk in a Spanish population. Moreover, we show for the first time that both these alleles regulate differentially the amount of a reporter gene (luciferase) in an in vitro assay on HeLa cells. These findings suggest that both these SNPs may have a functional role in regulating the expression of CD-86 and INSR proteins acting at the level of the 3'UTR. More functional studies are needed in order to better understand the role of polymorphic regulatory sequences at the 3'UTR of genes.
Authors:
Debora Landi; Victor Moreno; Elisabeth Guino; Pavel Vodicka; Barbara Pardini; Alessio Naccarati; Federico Canzian; Roberto Barale; Federica Gemignani; Stefano Landi
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Publication Detail:
Type:  Journal Article     Date:  2010-10-30
Journal Detail:
Title:  Mutation research     Volume:  717     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  109-15     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
Affiliation:
Dipartimento di Biologia, University of Pisa, Via Derna, 1, 56126 Pisa, Italy.
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