A Limited Set of Human MicroRNA Is Deregulated in Follicular Thyroid Carcinoma

Abstract

Context: Although the pathogenesis of follicular thyroid carcinoma (FTC) and its relation to follicular adenoma (FA) remains unclear, detailed understanding of FTC carcinogenesis would facilitate addressing the scientific and clinical challenges, given that there are morphological and molecular similarities between FTC and the frequently occurring FA. Micro-RNAs (miRNAs) are a new class of small, noncoding RNAs implicated in development and cancer and may lend novel clues to FTC genesis. For the latter process, a deregulated miRNA can orchestrate the aberrant expression of several hundred target genes. Objective: The objective of the study was to identify deregulated miRNAs in FTC. Design: We used two high-density expression arrays to identify miRNAs and their target genes that are differentially expressed between FTC and FA. Validation was done by quantitative RT-PCR. We further functionally characterized the effect of deregulated miRNAs in vitro using HEK293T, FTC133, and K5 cell lines. Patients: In total, 45 primary thyroid samples (23 FTC, 20 FA, four normal control thyroid) were analyzed. Results: Two specific miRNAs, miR-197 and miR-346, were significantly overexpressed in FTC. In vitro overexpression of either miRNA induced proliferation, whereas inhibition led to growth arrest. Overexpression of miR-197 and miR-346 repressed the expression of their predicted target genes in vitro and in vivo. Conclusions: Our observations show that miR-197 and miR-346 contribute to FTC carcinogenesis. Both miRNAs and their target genes might potentially provide for novel molecular markers and act as novel targets for treatment by interference, which could potentially normalize the deregulated profile of many downstream target genes.