Expressions of miRNAs in papillary thyroid carcinoma and their associations with the BRAFV600E mutation

Abstract

Objective: Alterations in microRNA (miRNA) expression have been described in thyroid tumors, suggesting a role for miRNAs in thyroid carcinogenesis. BRAF^V600E is the most frequently identified genetic alteration in papillary thyroid carcinoma (PTC). We investigated the link between BRAF^V600E status and the expression of miRNAs in PTC and analyzed the associations of these factors with clinicopathological characteristics.Design and methods: Prospective study of patients who underwent thyroid surgery between October 8, 2008 and November 1, 2010. BRAF^V600E status was determined by mutant allele-specific amplification PCR and direct sequencing of exon 15 of the BRAF gene in 69 PTC tissues and 69 respective paracancerous normal thyroid tissues. Initially, miRNA expression was analyzed in 12 PTC tissues and three associated paracancerous tissues using a miRNA microarray. miRNAs differentially expressed between BRAF^V600E-positive and -negative PTC tissues were then validated by real-time quantitative PCR on 69 PTC tissues and 69 paracancerous tissues. We also explored the associations between BRAF^V600E status or differential miRNA expression and clinicopathological characteristics.Results: The mutation rate of BRAF^V600E in PTC was 47.8%. Twelve miRNAs were upregulated and six were downregulated in PTC tissues, among which miR-15a, 15a*, 34a*, 34b*, 551b, 873, 876-3p, and 1274a were first identified. miR-21* and 203 were significantly dysregulated (PBRAF^V600E. Additionally, there were significant associations (PBRAF^V600E and a higher tumor–node–metastasis staging (III/IV), and between miR-21* over-expression and lymph node metastasis.Conclusions: We identified two miRNAs that are differentially expressed in PTC tissues with BRAF^V600E and revealed their associations with clinicopathological features. These findings may lead to the development of a potential diagnostic biomarker or prognostic indicator of PTC.