American Association for Cancer Research
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Supplementary Figure Legends from Thyroid Hormone Regulation of miR-21 Enhances Migration and Invasion of Hepatoma

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journal contribution
posted on 2023-03-30, 22:04 authored by Ya-Hui Huang, Yang-Hsiang Lin, Hsiang-Cheng Chi, Chen-Hsin Liao, Chia-Jung Liao, Sheng-Ming Wu, Cheng-Yi Chen, Yi-Hsin Tseng, Chung-Ying Tsai, Sheng-Yen Lin, Yu-Ting Hung, Chih-Jen Wang, Crystal D. Lin, Kwang-Huei Lin

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Thyroid hormone (T3) signaling through the thyroid hormone receptor (TRα1) regulates hepatoma cell growth and pathophysiology, but the underlying mechanisms are unclear at present. Here, we have shown that the oncomir microRNA-21 (miR-21) is activated by T3 through a native T3 response element in the primary miR-21 promoter. Overexpression of miR-21 promoted hepatoma cell migration and invasion, similar to that observed with T3 stimulation in hepatoma cells. In addition, anti-miR-21–induced suppression of cell migration was rescued by T3. The Rac-controlled regulator of invasion and metastasis, T-cell lymphoma invasion and metastasis 1 (TIAM1), was identified as a miR-21 target additionally downregulated by T3. Attenuation and overexpression of miR-21 induced upregulation and downregulation of TIAM1, respectively. TIAM1 attenuation, in turn, enhanced migration and invasion via the upregulation of β-catenin, vimentin, and matrix metalloproteinase-2 in hepatoma cells. Notably, correlations between TRα1, miR-21, and TIAM1 expression patterns in animal models paralleled those observed in vitro. In the clinic, we observed a positive correlation (P = 0.005) between the tumor/nontumor ratios of TRα1 and miR-21 expression, whereas a negative correlation (P = 0.019) was seen between miR-21 and TIAM1 expression in patients with hepatoma. Our findings collectively indicate that miR-21 stimulation by T3 and subsequent TIAM1 suppression promotes hepatoma cell migration and invasion. Cancer Res; 73(8); 2505–17. ©2013 AACR.