BRAFV600E, BANCR, miR-203a-3p and miR-204-3p in Risk Stratification of PTC Patients

Author:

Stojanović Stefana1,Šelemetjev Sonja1ORCID,Đorić Ilona1,Janković Miljuš Jelena1,Tatić Svetislav2,Živaljević Vladan3,Išić Denčić Tijana1ORCID

Affiliation:

1. Department of Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy—INEP, University of Belgrade, Banatska 31b, 11000 Belgrade, Serbia

2. Institute for Pathology, Faculty of Medicine, University of Belgrade, Doctor Subotic Street 1, 11000 Belgrade, Serbia

3. Clinic for Endocrine Surgery, University Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia

Abstract

In order to enhance the risk stratification of papillary thyroid carcinoma (PTC) patients, we assessed the presence of the most common mutation in PTC (BRAFV600E) with the expression profiles of long non-coding RNA activated by BRAFV600E (BANCR) and microRNAs, which share complementarity with BANCR (miR-203a-3p and miR-204-3p), and thereafter correlated it with several clinicopathological features of PTC. BRAFV600E was detected by mutant allele-specific PCR amplification. BANCR and miRs levels were determined by quantitative RT-PCR. Bioinformatic analysis was applied to determine the miRs’ targets. The expression profile of miR-203a-3p/204-3p in PTC was not affected by BRAFV600E. In the BRAFV600E-positive PTC, high expression of miR-203a-3p correlated with extrathyroidal invasion (Ei), but the patients with both high miR-203a-3p and upregulated BANCR were not at risk of Ei. In the BRAFV600E-negative PTC, low expression of miR-204-3p correlated with Ei, intraglandular dissemination and pT status (p < 0.05), and the mutual presence of low miR-204-3p and upregulated BANCR increased the occurrence of Ei. Bioinformatic analysis predicted complementary binding between miR-203a-3p/204-3p and BANCR. The co-occurrence of tested factors might influence the spreading of PTC. These findings partially describe the complicated network of interactions that may occur during the development of PTC aggressiveness, potentially providing a new approach for high-risk PTC patient selection.

Funder

Ministry of Science, Technological Development and Innovation of the Republic of Serbia

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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