Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma
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- 20 May 2008
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 105 (20), 7269-7274
- https://doi.org/10.1073/pnas.0802682105
Abstract
Although papillary thyroid carcinoma (PTC) displays strong heritability, no predisposing germ-line mutations have been found. We show that a common G/C polymorphism (rs2910164) within the pre-miR-146a sequence reduced the amount of pre- and mature miR-146a from the C allele 1.9- and 1.8-fold, respectively, compared with the G allele. This is matched by a similar decrease in the amount of each pre-miR generated from the corresponding pri-miR-146a in an in vitro processing reaction. The C allele also interfered with the binding of a nuclear factor to pre-miR-146a. The reduction in miR-146a led to less efficient inhibition of target genes involved in the Toll-like receptor and cytokine signaling pathway (TRAF6, IRAK1), and PTC1 (also known as CCDC6 or H4), a gene frequently rearranged with RET proto-oncogene in PTC. In an association study of 608 PTC patients and 901 controls, we found marked differences in genotype distribution of rs2910164 (P = 0.000002), the GC heterozygous state being associated with an increased risk of acquiring PTC (odds ratio = 1.62, P = 0.000007), and both homozygous states protective with odds ratio = 0.42 for the CC genotype (P = 0.003) and odds ratio = 0.69 for the GG genotype (P = 0.0006). Moreover, 4.7% of tumors had undergone somatic mutations of the SNP sequence. Thus, our data suggest that a common polymorphism in pre-miR-146a affects the miR expression, contributes to the genetic predisposition to PTC, and plays a role in the tumorigenesis through somatic mutation. Preliminary evidence suggests that these effects are mediated through target genes whose expression is affected by the SNP status.Keywords
This publication has 53 references indexed in Scilit:
- Epstein-Barr Virus Latent Membrane Protein 1 Induces Cellular MicroRNA miR-146a, a Modulator of Lymphocyte Signaling PathwaysJournal of Virology, 2008
- Cancer Statistics, 2007CA: A Cancer Journal for Clinicians, 2007
- MicroRNA Signatures in Human CancersNature Reviews Cancer, 2006
- NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responsesProceedings of the National Academy of Sciences, 2006
- A Novel Assay for Viral MicroRNA Function Identifies a Single Nucleotide Polymorphism That Affects Drosha ProcessingJournal of Virology, 2006
- Oncomirs — microRNAs with a role in cancerNature Reviews Cancer, 2006
- MicroRNA expression profiles classify human cancersNature, 2005
- Comparison of real-time PCR methods for detection of Salmonella enterica and Escherichia coli O157:H7, and introduction of a general internal amplification controlJournal of Microbiological Methods, 2004
- Fast and effective prediction of microRNA/target duplexesRNA, 2004
- NF-κB at the crossroads of life and deathNature Immunology, 2002