卵巢癌（OC）是全球妇科肿瘤相关死亡的第二大原因。N6-甲基腺苷（m6A）是真核生物RNA中最丰富的内部修饰。人类胰岛素样生长因子2 mRNA结合蛋白2（IGF2BP2）是一种m6A阅读蛋白，通过识别m6A修饰来增强mRNA稳定性并促进翻译。其在多种癌症中具有促癌作用。然而，m6A修饰和IGF2BP2在OC中的作用目前尚不清楚。本研究通过使用甲基化RNA免疫沉淀测序技术，证明了OC组织中m6A修饰普遍失调。OC中的m6A修饰以及IGF2BP2的mRNA和蛋白水平均显著升高。IGF2BP2过表达促进了OC细胞的增殖、迁移和侵袭，并在体内促进肿瘤生长和转移。而IGF2BP2敲除则显示相反效果。在机制上，我们确定了细胞骨架相关蛋白类似物2（CKAP2L）是IGF2BP2的靶标。IGF2BP2促进了CKAP2L的m6A依赖性翻译，而不影响mRNA和蛋白稳定性。通过过表达CKAP2L可拯救OC细胞中IGF2BP2敲除的抑制肿瘤效应。总之，本研究揭示了IGF2BP2在肿瘤进展中的潜在作用，至少部分通过促进m6A依赖性方式翻译CKAP2L。© 2023美国实验生物学协会。

Ovarian cancer (OC) is the second leading cause of gynecological cancer-related death in women worldwide. N6-methyladenosine (m6 A) is the most abundant internal modification in eukaryotic RNA. Human insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an m6 A reader, can enhance mRNA stability and promote translation by recognizing m6 A modifications. Its tumor-promoting effects have been demonstrated in several cancers. However, the roles of m6 A modification and IGF2BP2 in OC remain unclear. Here, by using methylated RNA immunoprecipitation sequencing, we demonstrated that there is widespread dysregulation of m6 A modification in OC tissues. The m6 A modification and the mRNA and protein levels of IGF2BP2 were significantly elevated in OC. Overexpression of IGF2BP2 facilitated OC cell proliferation, migration, and invasion in vitro and accelerated tumor growth and metastasis in vivo. While IGF2BP2-knockdown showed the opposite effect. Mechanistically, we identified cytoskeleton-associated protein 2-like (CKAP2L) as a target of IGF2BP2. IGF2BP2 promoted CKAP2L translation dependent on m6 A modification, rather than affecting mRNA and protein stability. Overexpression of CKAP2L rescued the tumor-suppressive effect of IGF2BP2 knockdown in OC cells. In conclusion, this study revealed the potential role of IGF2BP2 in tumor progression, at least partially via promoting the translation of CKAP2L in an m6 A-dependent manner.© 2023 Federation of American Societies for Experimental Biology.