Papillary thyroid cancer (PTC) is the main histological type of thyroid cancer and accounts for almost all increased cases worldwide. Patients with PTC exhibit a favorable prognosis, but the fact that PTC is often accompanied by a high prevalence of lymph node metastasis (LNM) means that the overall recurrence-free survival rate in PTC patients is relatively low. Herein, we identified that ID3 expression is subdued in PTC tissues and closely associated with LNM and a poor disease-free survival outcome in PTC patients. The main contributor to this gene repression is the hypermethylation of the CpG island at the promoter of ID3. Besides, we uncovered that a loss of ID3 promotes invasion and migration of PTC cells, while an ectopic overexpression of ID3 inhibits invasion and migration. Mechanistically, ID3 exhibits tumor suppressor functions in PTC cells by interacting with E47 to form heterodimers that prevent E47 binding to CDH1 promoter and maintaining CDH1 transcription and epithelial phenotype in PTC cells. Taken together, our study demonstrates that ID3 plays a tumor suppressor role in PTC and impedes metastasis by inhibiting E47-mediated epithelial to mesenchymal transition.

甲状腺乳头状癌 (PTC) 是甲状腺癌的主要组织学类型，几乎占全球所有病例增加的原因。PTC 患者的预后良好，但 PTC 常伴有淋巴结转移 (LNM) 的高患病率，这意味着 PTC 患者的总体无复发生存率相对较低。在此，我们发现 ID3 表达在 PTC 组织中受到抑制，并且与 LNM 和 PTC 患者的无病生存结果不佳密切相关。这种基因抑制的主要因素是 ID3 启动子处 CpG 岛的高甲基化。此外，我们发现 ID3 的缺失促进了 PTC 细胞的侵袭和迁移，而 ID3 的异位过表达抑制了侵袭和迁移。从机制上讲，ID3 通过与 E47 相互作用形成异二聚体，阻止 E47 与 CDH1 启动子结合并维持 PTC 细胞中的 CDH1 转录和上皮表型，从而在 PTC 细胞中表现出肿瘤抑制功能。总之，我们的研究表明 ID3 在 PTC 中发挥肿瘤抑制作用，并通过抑制 E47 介导的上皮向间充质转化来阻止转移。