<scp>LncRNA GAS5</scp> sponges <scp>miR</scp>‐362‐5p to promote sensitivity of thyroid cancer cells to <scp>¹³¹I</scp> by upregulating <scp>SMG1</scp>

Abstract

This study aims to investigate the role of lncRNA growth arrest-specific transcript 5 (GAS5)/miR-362-5p/suppressor of morphogenesis in the genitalia 1 (SMG1) axis in ¹³¹ I-resistance in thyroid cancer (TC). GAS5, miR-362-5p, and SMG1 expression in TC tissues was assessed and the ¹³¹ I-resistant TC cells were established, which were treated with altered GAS5, miR-362-5p, and SMG1. The proliferation and apoptosis of ¹³¹ I-resistant TC cells were detected, and the expression of Akt/mTOR signaling pathway-related proteins was assessed. Binding relations between GAS5 and miR-362-5p, and miR-362-5p and SMG1 were confirmed. The role of GAS5 in ¹³¹ I-resistant TC cell growth in vivo was observed. GAS5 was downregulated and miR-362-5p was upregulated in TC tissues and ¹³¹ I-resistant cells. The ¹³¹ I-resistant TC cells had enhanced proliferation and repressed apoptosis, and the Akt/mTOR signaling pathway was activated. Overexpressed GAS5 strengthened ¹³¹ I sensitivity and suppressed TC cell growth, while upregulated miR-362-5p had an opposite effect. MiR-362-5p upregulation reversed the effect of GAS5, and SMG1 overexpression eliminated the impact of miR-362-5p upregulation on ¹³¹ I-resistant TC cells. GAS5 competitively binds to miR-362-5p and SMG1 is targeted by miR-362-5p. GAS5 sponges miR-362-5p to promote sensitivity of TC cells to ¹³¹ I by upregulating SMG1 and inactivating Akt/mTOR signaling pathway.