Unknown

Dataset Information

0

Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma.


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.

SUBMITTER: Jazdzewski K 

PROVIDER: S-EPMC2438239 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma.

Jazdzewski Krystian K   Murray Elizabeth L EL   Franssila Kaarle K   Jarzab Barbara B   Schoenberg Daniel R DR   de la Chapelle Albert A  

Proceedings of the National Academy of Sciences of the United States of America 20080512 20


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 a  ...[more]

Similar Datasets

| S-EPMC4667020 | biostudies-literature
| S-EPMC3847917 | biostudies-literature
| S-EPMC2635764 | biostudies-literature
| S-EPMC3579867 | biostudies-literature
| S-EPMC10854783 | biostudies-literature
| S-EPMC4726409 | biostudies-literature
| S-EPMC5877516 | biostudies-literature
| S-EPMC6162394 | biostudies-literature
| S-EPMC6044525 | biostudies-literature
| S-EPMC3518668 | biostudies-literature