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Expression profiles of pivotal microRNAs and targets in thyroid papillary carcinoma: an analysis of The Cancer Genome Atlas

Authors Cong D, He MZ, Chen SL, Liu XL, Liu XD, Sun H

Received 31 March 2015

Accepted for publication 11 June 2015

Published 26 August 2015 Volume 2015:8 Pages 2271—2277

DOI https://doi.org/10.2147/OTT.S85753

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Editor who approved publication: Professor Daniele Santini

Dan Cong,1 Mengzi He,2 Silin Chen,2 Xiaoli Liu,1 Xiaodong Liu,2 Hui Sun1

1Jilin Provincial Key Laboratory of Surgical Translational Medicine, Department of Thyroid and Parathyroid Surgery, People’s Republic of China–Japan Union Hospital, 2Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, Jilin, People’s Republic of China

Abstract: In the present study, we analyzed microRNA (miRNA) and gene expression profiles using 499 papillary thyroid carcinoma (PTC) samples and 58 normal thyroid tissues obtained from The Cancer Genome Atlas database. A pivotal regulatory network of 18 miRNA and 16 targets was identified. Upregulated miRNAs (miR-222, miR-221, miR-146b, miR-181a/b/d, miR-34a, and miR-424) and downregulated miRNAs (miR-9-1, miR-138, miR-363, miR-20b, miR-195, and miR-152) were identified. Among them, the upregulation of miR-424 and downregulation of miR-363, miR-195, and miR-152 were not previously identified. The genes CCNE2 (also known as cyclin E2), E2F1, RARA, CCND1 (cyclin D1), RUNX1, ITGA2, MET, CDKN1A (p21), and COL4A1 were overexpressed, and AXIN2, TRAF6, BCL2, RARB, HSP90B1, FGF7, and PDGFRA were downregulated. Among them, CCNE2, COL4A1, TRAF6, and HSP90B1 were newly identified. Based on receiver operating characteristic curves, several miRNAs (miR-222, miR-221, and miR-34a) and genes (CCND1 and MET) were ideal diagnostic indicators, with sensitivities and specificities greater than 90%. The combination of inversely expressed miRNAs and targets improved diagnostic accuracy. In a clinical feature analysis, several miRNAs (miR-34a, miR-424, miR-20b, and miR-152) and genes (CCNE2, COL4A1, TRAF6, and HSP90B1) were associated with aggressive clinical features, which have not previously been reported. Our study not only identified a pivotal miRNA regulatory network associated with PTC but also provided evidence that miRNAs and target genes can be used as biomarkers in PTC diagnosis and clinical risk evaluation.

Keywords: thyroid carcinoma, miR-34a, miR-424, miR-20b, miR-152

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