文章：

m6A阅读蛋白IGF2BP2通过稳定DPP4促进甲状腺乳头状癌的淋巴转移

m6A reader IGF2BP2 promotes lymphatic metastasis by stabilizing DPP4 in papillary thyroid carcinoma 

原文发布日期：2023-12-15 

英文摘要：

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. 

摘要翻译： 

淋巴结转移是甲状腺乳头状癌局部复发的主要原因，但其发生机制尚不明确。N6-甲基腺苷（m6A）RNA修饰异常在癌症进展和转移中起关键作用，然而m6A修饰是否调控甲状腺乳头状癌的淋巴结转移仍有待探索。本研究发现IGF2BP2在甲状腺乳头状癌中表达上调，且与淋巴结转移呈正相关。功能实验表明，敲低IGF2BP2可显著抑制甲状腺乳头状癌细胞的体外增殖和侵袭能力，而过表达则产生相反效应。此外，体内实验证实IGF2BP2敲低能显著抑制淋巴转移。机制研究表明，通过人类m6A表观转录组芯片、MeRIP和RIP实验证实，IGF2BP2以m6A依赖性方式增强DPP4稳定性，从而激活NF-κB通路。值得注意的是，敲低IGF2BP2在一定程度上提高了甲状腺乳头状癌细胞对顺铂治疗的敏感性，而其过表达则产生相反效果。本研究揭示了IGF2BP2通过m6A依赖性方式稳定DPP4促进淋巴转移的机制，为理解甲状腺乳头状癌淋巴转移的分子机制提供了新视角。

原文链接：

m6A reader IGF2BP2 promotes lymphatic metastasis by stabilizing DPP4 in papillary thyroid carcinoma