IGF2BP2 promotes ovarian cancer growth and metastasis via upregulating CKAP2L protein expression in a m6A-dependent manner

Abstract

Abstract Ovarian cancer (OC) is the second leading cause of gynecologic cancer death in women around the world. N6-methyladenosine (m6A) is the most abundant internal modification on eukaryotic RNA. Human insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), as an m6A reader, can enhance mRNA stability and promote translation by recognizing m6A modifications. Its carcinogenic effect has been demonstrated in colon cancer, hepatocellular carcinoma, pancreatic cancer and other tumors. Here, we demonstrated that there was widespread dysregulation of m6A modification in OC tissues. The m6A modification, mRNA and protein level of IGF2BP2 were significantly elevated in OC. Overexpression of IGF2BP2 facilitated OC cell proliferation, migration, invasion in vitro and accelerated tumor growth and metastasis in vivo. Mechanistically, CKAP2L was a target mRNA of IGF2BP2. Unlike previous studies, IGF2BP2 promoted CKAP2L translation depending on m6A modification rather than affect mRNA and protein stability. Knockdown of CKAP2L rescued the oncogenic effect of IGF2BP2 in OC cells. In conclusion, this study unveiled the oncogenic role of IGF2BP2 potentially through promoting the translation of CKAP2L in a m6A dependent manner.