The rs2910164 Genetic Variant of miR-146a-3p Is Associated with Increased Overall Mortality in Patients with Follicular Variant Papillary Thyroid Carcinoma

International Journal of Molecular Sciences
Marta KotlarekAnna Wójcicka

Abstract

Aberrant expression of the sodium-iodide symporter (NIS) and the resistance to post-operative radioactive iodide treatment is a crucial cause of higher mortality of some thyroid cancer patients. In this study, we analyzed the impact of miR-146a on the expression and function of NIS and on the overall survival of thyroid cancer patients. The study included 2441 patients (2163 women; 278 men); including 359 cases with follicular variant of papillary thyroid carcinoma (fvPTC). miR:NIS interactions were analyzed in cell lines using in vivo binding and inhibition assays and radioactive iodine uptake assays. Tumor/blood DNA was used for rs2910164 genotyping. Overall survival was assessed retrospectively. In the results, we showed that miR-146a-3p directly binds to and inhibits NIS. Inhibition of miR-146a-3p restores the expression and function of NIS, increasing radioactive iodine uptake. Rs2910164 functional variant within miR-146a-3p is associated with increased overall mortality among fvPTC female patients. The deaths per 1000 person-years were 29.7 in CC carriers vs. 5.08 in GG/GC-carriers (HR = 6.21, p = 0.006). Higher mortality of CC vs. GG/GC carriers was also observed in patients with lower clinical stage (HR = 22.72, p < 0.0...Continue Reading

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Citations

Oct 24, 2018·International Journal of Cancer. Journal International Du Cancer·Jarosław JendrzejewskiAlbert de la Chapelle
Jan 9, 2019·Frontiers in Oncology·Han-Xi DingQian Xu
Sep 17, 2020·Cancers·Cristina Alina SilaghiCarmen Emanuela Georgescu
Jul 3, 2021·International Journal of Molecular Sciences·Wojciech GierlikowskiMarta Kotlarek-Łysakowska

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Methods Mentioned

BETA
genotyping
PCR

Software Mentioned

GraphPad Prism
TargetScan
R
STATISTICA

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