Lymph node metastasis (LNM) is a major cause of locoregional recurrence of papillary thyroid carcinoma (PTC). However, the mechanisms responsible for LNM are unclear. Aberrant N6-methyladenosine (m6A) RNA modification plays a vital role in cancer progression and metastasis, and whether m6A modification regulates LNM in PTC remains to be determined. This study showed that IGF2BP2 was upregulated in PTC and positively associated with LNM. Functionally, IGF2BP2 knockdown significantly inhibited PTC cell proliferation and invasion in vitro, and vice versa. Moreover, IGF2BP2 knockdown significantly inhibited lymphatic metastasis in vivo. Mechanistically, Human m6A epitranscriptomic microarray, MeRIP, and RIP assays demonstrated that IGF2BP2 activated the NF-KB pathway by enhancing DPP4 stability in an m6A-dependent manner. Furthermore, IGF2BP2 knockdown increased the sensitivity of PTC cells to cisplatin therapy to a certain extent, while its overexpression produced the opposite effects. Overall, this study uncovers that IGF2BP2 promotes lymphatic metastasis via stabilizing DPP4 in an m6A-dependent manner, and provides new insights for understanding the mechanism of lymphatic metastasis in PTC.

淋巴结转移（LNM）是甲状腺乳头状癌（PTC）局部复发的主要原因。然而，导致 LNM 的机制尚不清楚。异常的 N6-甲基腺苷 (m6A) RNA 修饰在癌症进展和转移中起着至关重要的作用，m6A 修饰是否调节 PTC 中的 LNM 仍有待确定。这项研究表明 IGF2BP2 在 PTC 中表达上调，并与 LNM 呈正相关。从功能上来说，IGF2BP2敲低可显着抑制体外PTC细胞的增殖和侵袭，反之亦然。此外，IGF2BP2敲低显着抑制体内淋巴转移。从机制上讲，人类 m6A 表观转录组微阵列、MeRIP 和 RIP 测定表明 IGF2BP2 通过以 m6A 依赖性方式增强 DPP4 稳定性来激活 NF-KB 通路。此外，IGF2BP2的敲低在一定程度上增加了PTC细胞对顺铂治疗的敏感性，而IGF2BP2的过表达则产生相反的效果。总体而言，本研究发现IGF2BP2以m6A依赖性方式通过稳定DPP4促进淋巴转移，为理解PTC淋巴转移机制提供了新的见解。