Selumetinib Activity in Thyroid Cancer Cells: Modulation of Sodium Iodide Symporter and Associated miRNAs

International Journal of Molecular Sciences
Sabine WächterPietro Di Fazio

Abstract

The MEK (mitogen-activated protein kinase)⁻inhibitor selumetinib led to increased radioiodine uptake and retention in a subgroup of patients suffering from radioiodine refractory differentiated thyroid cancer (RR-DTC). We aimed to analyse the effect of selumetinib on the expression of sodium iodide symporter (NIS; SLC5A5) and associated miRNAs in thyroid cancer cells. Cytotoxicity was assessed by viability assay in TPC1, BCPAP, C643 and 8505C thyroid cancer cell lines. NIS, hsa-let-7f-5p, hsa-miR-146b-5p, and hsa-miR-146b-3p expression was determined by quantitative RT-PCR. NIS protein was detected by Western blot. Radioiodine uptake was performed with a Gamma counter. Selumetinib caused a significant reduction of cell viability in all thyroid cancer cell lines. NIS transcript was restored by selumetinib in all cell lines. Its protein level was found up-regulated in TPC1 and BCPAP cells and down-regulated in C643 and 8505C cells after treatment with selumetinib. Treatment with selumetinib caused a down-regulation of hsa-let-7f-5p, hsa-miR-146b-5p and hsa-miR-146b-3p in TPC1 and BCPAP cells. In 8505C cells, a stable or down-regulated hsa-miR-146b-5p was detected after 1h and 48h of treatment. C643 cells showed stable or up-regul...Continue Reading

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Citations

Jul 6, 2020·Cancer Biomarkers : Section a of Disease Markers·Kevin SheeAngeline S Andrew
Jul 5, 2019·International Journal of Molecular Sciences·Livia ManzellaPaolo Vigneri
Jun 16, 2019·International Journal of Molecular Sciences·Daniela Grimm
Oct 11, 2019·Current Opinion in Oncology·Stefania BulottaDiego Russo
Feb 16, 2021·Endocrine·Stefania BulottaValentina Maggisano

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Methods Mentioned

BETA
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PCR

Software Mentioned

R
CFX Manager
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1D

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