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

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.

Circular RNA CircPPP1CB Suppresses Tumorigenesis by Interacting With the MiR-1307-3p/SMG1 Axis in Human Bladder Cancer

“…Mechanically, the circPPP1CB/miR-1307-3p axis directly targeted SMG1 to modulate biological functions. SMG1, a member of the phosphoinositide 3-kinaserelated kinases family, acted as a novel tumor suppressor in various human cancers (Du et al, 2014;Mai et al, 2019;Yin et al, 2019;Li et al, 2020). In our study, we confirmed that SMG1 remarkably suppressed cell proliferation, migration, invasion, and tumor angiogenesis of BC.…”

“…Loss of SMG1 completely leads to early embryonic lethal, but mice with SMG1 haploinsufficiency represent a predisposition to chronic inflammation, oxidative stress, and tumorigenesis (Roberts et al, 2013). Meanwhile, a growing body of evidence has confirmed that SMG1 acted as a tumor suppressor in various human cancers (Gubanova et al, 2013;Du et al, 2014;Han et al, 2014;Zhang et al, 2018;Mai et al, 2019;Li et al, 2020).…”