Department of Thyroid-Head and Neck Oncosurgery-1, Jilin Cancer Hospital, Changchun, Jilin Province, China.
Department of Thoracic Oncosurgery-1, Jilin Cancer Hospital, Changchun, Jilin Province, China.
Aging (Albany NY). 2023 Nov 21;15(22):13542-13557. doi: 10.18632/aging.205284.
Thyroid cancer is a prevalent endocrine malignancy around the world. Radioactive iodine (I) therapy is widely applied in TC patients, but the resistance affects its effectiveness in the clinics. Long non-coding RNA (lncRNA) EGOT has been reported to induce an inhibitory effect on cancer progression, but the specific function of EGOT in I resistance of TC cells remains unclear. Here, we successfully established I-resistant TC cells and evaluated the impact of EGOT on I resistance in the cells. Our data showed that EGOT and PTEN expression was reduced but the miR-641 expression was enhanced in I-resistant TC cells. EGOT inhibited viability, induced apoptosis and enhanced DNA damage in I-resistant TC cells. Mechanically, we identified that EGOT induced PTEN expression by targeting miR-641 in 131I-resistant TC cells. Moreover, the depletion of PTEN and miR-641 mimic reversed EGOT-relieved I resistance of TC cells . Thus, we conclude that lncRNA EGOT attenuated I resistance of TC cells by targeting miR-641/PTEN axis. The clinical functions of EGOT in TC therapy deserve to be validated in future exploration.
甲状腺癌是一种全球范围内常见的内分泌恶性肿瘤。放射性碘（I）治疗广泛应用于 TC 患者，但耐药性影响了其在临床上的疗效。长链非编码 RNA（lncRNA）EGOT 已被报道对癌症进展具有抑制作用，但 EGOT 在 TC 细胞 I 耐药中的具体作用尚不清楚。在这里，我们成功建立了 I 耐药 TC 细胞，并评估了 EGOT 对细胞 I 耐药的影响。我们的数据表明，在 I 耐药 TC 细胞中，EGOT 和 PTEN 的表达降低，而 miR-641 的表达增强。EGOT 抑制 I 耐药 TC 细胞的活力，诱导细胞凋亡，并增强 DNA 损伤。在机制上，我们确定 EGOT 通过靶向 miR-641 在 131I 耐药 TC 细胞中诱导 PTEN 表达。此外，PTEN 耗竭和 miR-641 模拟物的恢复逆转了 EGOT 减轻 TC 细胞 I 耐药的作用。因此，我们得出结论，lncRNA EGOT 通过靶向 miR-641/PTEN 轴减轻 TC 细胞的 I 耐药性。EGOT 在 TC 治疗中的临床作用值得在未来的探索中进一步验证。
