miR-221-3p and miR-222-3p regulate the SOCS3/STAT3 signaling pathway to downregulate the expression of NIS and reduce radiosensitivity in thyroid cancer

Ting Ye; Lili Zhong; Xuemei Ye; Jie Liu; Linfa Li; Heqing Yi

doi:10.3892/etm.2021.10084

miR-221-3p and miR-222-3p regulate the SOCS3/STAT3 signaling pathway to downregulate the expression of NIS and reduce radiosensitivity in thyroid cancer

Exp Ther Med. 2021 Jun;21(6):652. doi: 10.3892/etm.2021.10084. Epub 2021 Apr 19.

Authors

Ting Ye^{1

2}, Lili Zhong³, Xuemei Ye^{1

2}, Jie Liu^{1

2}, Linfa Li^{1

2}, Heqing Yi^{1

2}

Affiliations

¹ Department of Nuclear Medicine, Key Laboratory of Head and Neck Cancer Translational Research of Zhejiang Province, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang 310021, P.R. China.
² Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang 310021, P.R. China.
³ Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, Second Hospital of Jilin University, Changchun, Jilin 130022, P.R. China.

Abstract

The expression levels of microRNA (miR)-221-3p and miR-222-3p in thyroid cancer have been found to be upregulated compared with those in normal tissues. The present study aimed to determine the effects and potential underlying mechanisms of miR-221-3p and miR-222-3p on the regulation of radioactive iodine (¹³¹I) uptake and radiosensitivity of thyroid cancer cells. The potential regulatory target genes of miR-221-3p and miR-222-3p were predicted by bioinformatics analysis, and reverse transcription-quantitative polymerase chain reaction was used to verify miR-221-3p, miR-222-3p and target gene expression levels in thyroid cancer tissues and cell lines. Overexpression of miR-221-3p or miR-222-3p in cell models was performed using lentivirus infection. Knockdown of miR-221-3p and miR-222-3p in cells was achieved using oligonucleotide inhibitor transfection. Western blotting was used to analyze the expression levels of target proteins. In addition, the effects of miR-221-3p and miR-222-3p on the radiosensitivity of thyroid cancer cells were verified using a colony formation assay. The results of the present study revealed that the expression levels of miR-221-3p and miR-222-3p were significantly upregulated, while the expression levels of suppressor of cytokine signaling 3 (SOCS3) were downregulated in thyroid cancer tissues. Furthermore, miR-221-3p and miR-222-3p overexpression downregulated the expression levels of SOCS3, E-cadherin and solute carrier family 5 member 5 (NIS), and upregulated the expression levels of phosphorylated STAT3 and vimentin. Following the overexpression of miR-221-3p or miR-222-3p in the FTC133 and TPC1 cell lines, their radiosensitivity was suppressed. In conclusion, the findings of the present study suggested that miR-221-3p and miR-222-3p may downregulate the expression levels of NIS and promote radioresistance. The potential mechanism was hypothesized to be associated with the miR-221-3p and miR-222-3p targeting of the SOCS3 gene, which may subsequently activate the STAT3 signaling pathway.

Keywords: differentiated thyroid cancer; microRNA-221; microRNA-222; radiosensitivity; solute carrier family 5 member 5; suppressor of cytokine signaling 3.

Grants and funding

Funding: The present study was supported by the National Natural Science Foundation of China (grant no. 81502318) and the Zhejiang Province Natural Science Foundation of China (grant no. LY20H180007).