AUTHOR=Hou Shasha , Xie Xiaorui , Zhao Jing , Wu Cailan , Li Ning , Meng Zhaowei , Cai Chunquan , Tan Jian 

TITLE=Downregulation of miR-146b-3p Inhibits Proliferation and Migration and Modulates the Expression and Location of Sodium/Iodide Symporter in Dedifferentiated Thyroid Cancer by Potentially Targeting MUC20

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.566365

DOI=10.3389/fonc.2020.566365

ISSN=2234-943X

ABSTRACT=<p>The dedifferentiation of differentiated thyroid cancer (DTC) is a challenging problem for radioactive iodine (<sup>131</sup>I) treatment, also known as radioiodine refractory differentiated thyroid cancer (RAIR-DTC). The purpose of this study was to further explore the mechanism of the redifferentiation of dedifferentiated thyroid cancer. Ineffective and effective groups of <sup>131</sup>I therapy were analyzed and compared in both our clinical and TCGA samples. Whole-exome sequencing, mutation analysis, transcriptome analysis, and <italic>in vitro</italic> functional experiments were conducted. <italic>FLG</italic>, <italic>FRG1</italic>, <italic>MUC6</italic>, <italic>MUC20</italic>, and <italic>PRUNE2</italic> were overlapping mutation genes between our clinical cases, and the TCGA cases only appeared in the ineffective group. The expression of <italic>miR-146b-3p</italic> target <italic>MUC20</italic> was explored. The expression levels of <italic>miR-146b-3p</italic> and <italic>MUC20</italic> were significantly increased, and the inhibition of <italic>miR-146b-3p</italic> expression significantly inhibited proliferation and migration, promoted apoptosis, regulated the expression and location of thyroid differentiation-related genes, and sodium/iodide symporter (NIS) in dedifferentiated thyroid cancer cells (WRO). Thus, <italic>miR-146b-3p</italic> potentially targets <italic>MUC20</italic> participation in the formation of DTC dedifferentiation, resulting in resistance to <sup>131</sup>I and the loss of the iodine uptake ability of DTC cancer foci, promoting refractory differentiated thyroid cancer. <italic>miR-146b-3p</italic> may be a potentially therapeutic target for the reapplication of <sup>131</sup>I therapy in dedifferentiated thyroid cancer patients.</p>