Are pre-miR-146a and PTTG1 associated with papillary thyroid cancer?

Abstract

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, with a steadily increasing incidence in the last few decades worldwide. The predisposition to developing this carcinoma by the heterozygous state of rs2910164 within the precursor of the miR-146a has been reported, but recently not confirmed. Interestingly, on the same chromosome, almost 50 kb separate the pre-miR-146a from the pituitary tumor-transforming gene 1 (PTTG1), a proto-oncogene involved in several tumors, including thyroid cancers. In this study, we analyzed, using a case–control design, the genetic association between PTC and the genomic region encompassing pre-miR-146a rs2910164 and PTTG1 rs1862391 and rs2910202. We enrolled 307 affected patients and 206 healthy controls. The possible presence of thyroid nodules in controls was excluded by ultrasonography. All the cases were submitted to single-nucleotide polymorphism (SNP) genotyping of pre-miR-146a and PTTG1, and risk association analyses were carried out. The genotypic and allelic frequencies of pre-miR-146a rs2910164 were not statistically different in the patients and controls, and this SNP was not in linkage disequilibrium with the investigated PTTG1 SNPs. Consistently, meta-analyses, the first including all the affected cases published to date, did not confirm the previously reported association of the heterozygous CG genotype with PTC. The PTTG1 SNPs exhibited the same allelic frequency in the patients and controls and were not associated with the disease. In conclusion, in a well-selected Italian population, neither pre-miR-146a rs2910164 nor PTTG1 rs1862391 and rs2910202 were found to be associated with the risk of developing PTC.

Associations of Single Nucleotide Polymorphisms in miR-146a, miR-196a, miR-149 and miR-499 with Colorectal Cancer Susceptibility

“…This C > G polymorphism results in a change from C: U pair to G: U mismatch in the stem structure of miR-146a precursor. Several studies have been investigated the association of miR-146a rs2910164 polymorphism and risk of various cancer (Jazdzewski et al, 2008;Hu et al, 2009;Catucci et al, 2010;Okubo et al, 2010;Zeng et al, 2010;Garcia et al, 2011;Alshatwi et al, 2012;Hezova et al, 2012;Min et al, 2012;Zhou et al, 2012;Chae et al, 2013;Hu et al, 2013;Lv et al, 2013;Ma et al, 2013;Marino et al, 2013;Wei et al, 2013;Vinci et al, 2013). Our results did not support a genetic association between miR-146a rs2910164 and susceptibility to CRC.…”

MECHANISMS IN ENDOCRINOLOGY: MicroRNA in diagnostics and therapy of thyroid cancer

“…The rs2910164-mediated predisposition was further analyzed in 781 thyroid cancer patients recruited in the United Kingdom (28), and the study revealed no association between the polymorphism and thyroid cancer risk. Similar results were obtained in 753 Chinese patients (29) and in 307 Italian patients (30). However, meta-analyses revealed a strong association of the SNP with the cancer risk in the Caucasian population (30).…”

“…Similar results were obtained in 753 Chinese patients (29) and in 307 Italian patients (30). However, meta-analyses revealed a strong association of the SNP with the cancer risk in the Caucasian population (30). Interestingly, another study performed in FTC and follicular adenomas (FA) showed that the CC genotype within the rs2910164 was completely absent in FTC tumors.…”

miR-146a and miR-146b promote proliferation, migration and invasion of follicular thyroid carcinoma via inhibition of ST8SIA4

“…PTTG1, which is targeted by miR-146a and miR-146b, is also regulates thyroid cancer [35]. However, PTTG1 expression was not significantly altered in FTC-133 and FTC-238 cells when miR-146a and miR-146b were inhibited (data not shown).…”