Due to the steadily rising morbidity and mortality, thyroid cancer remains the most commonly seen endocrine cancer. The present study attempted to investigate the mechanism from the perspective of long non-coding RNA (lncRNA) regulation. We identified 53 markedly increased lncRNAs in thyroid cancer samples according to TCGA data. Among them, high lncRNA DIO3OS expression was a risk factor for thyroid cancer patients’ poorer overall survival. DIO3OS showed to be considerably increased within thyroid cancer tissue samples and cells. Knocking down DIO3OS within thyroid carcinoma cells suppressed cancer cell viability, the capacity of DNA synthesis, cell invasion, as well as cell migration; besides, proliferating markers, ki-67 and PCNA, were decreased by DIO3OS knockdown. Cancer bioinformatics analysis suggested that NF-κB2 might be related to DIO3OS function in thyroid cancer carcinogenesis. NF-κB2 was positively correlated with DIO3OS, and DIO3OS knockdown decreased NF-κB2 protein levels. Knocking down NF-κB2 within thyroid carcinoma cells suppressed cancer cell viability, the capacity of DNA synthesis, cell invasion, cell migration, and the protein levels of proliferating markers. Let-7d directly targeted DIO3OS and NF-κB2; DIO3OS knockdown upregulated let-7d expression. The overexpression of let-7d suppressed cancer cell viability, the capacity of DNA synthesis, cell invasion, cell migration, as well as the protein levels of proliferating markers. Let-7d inhibition remarkably attenuated the functions of DIO3OS knockdown in NF-κB2 expression and thyroid cancer cell phenotype. In conclusion, DIO3OS/let-7d/NF-κB2 axis regulates the viability, DNA synthesis capacity, invasion, and migration of thyroid cancer cells. The clinical application of this axis needs further in vivo and clinical investigation.

由于发病率和死亡率稳步上升，甲状腺癌仍然是最常见的内分泌癌。本研究试图从长期的非编码RNA（lncRNA）调控的角度研究这种机制。根据TCGA数据，我们在甲状腺癌样品中鉴定出53个lncRNA显着增加。其中，lncRNA DIO3OS高表达是甲状腺癌患者总体生存较差的危险因素。在甲状腺癌组织样本和细胞中，DIO3OS显着增加。在甲状腺癌细胞中敲低DIO3OS抑制了癌细胞的生存能力，DNA合成能力，细胞侵袭以及细胞迁移。此外，通过DIO3OS敲低，增殖标记ki-67和PC​​NA降低。癌症生物信息学分析表明，NF-κB2可能与DIO3OS在甲状腺癌致癌中的功能有关。NF-κB2与DIO3OS呈正相关，而DIO3OS敲低可降低NF-κB2蛋白水平。在甲状腺癌细胞中敲低NF-κB2抑制了癌细胞的生存能力，DNA合成能力，细胞侵袭能力，细胞迁移能力以及增殖标志物的蛋白质水平。Let-7d直接靶向DIO3OS和NF-κB2；DIO3OS组合式上调let-7d表达。let-7d的过表达抑制了癌细胞的活力，DNA合成的能力，细胞侵袭，细胞迁移以及增殖标志物的蛋白质水平。Let-7d抑制显着减弱DIO3OS敲低的NF-κB2表达和甲状腺癌细胞表型的功能。结论，DIO3OS / let-7d /NF-κB2轴调节甲状腺癌细胞的活力，DNA合成能力，侵袭和迁移。该轴的临床应用需要进一步的体内和临床研究。