IGF2BP2-modified circular RNA circARHGAP12 promotes cervical cancer progression by interacting m6A/FOXM1 manner

Abstract

Emerging evidence indicates that circular RNA (circRNA) and N6-methyladenosine (m6A) play critical roles in cervical cancer. However, the synergistic effect of circRNA and m6A on cervical cancer progression is unclear. In the present study, our sequencing data revealed that a novel m6A-modified circRNA (circARHGAP12, hsa_circ_0000231) upregulated in the cervical cancer tissue and cells. Interestingly, the m6A modification of circARHGAP12 could amplify its enrichment. Functional experiments illustrated that circARHGAP12 promoted the tumor progression of cervical cancer in vivo and vitro. Furthermore, MeRIP-Seq illustrated that there was a remarkable m6A site in FOXM1 mRNA. CircARHGAP12 interacted with m6A reader IGF2BP2 to combine with FOXM1 mRNA, thereby accelerating the stability of FOXM1 mRNA. In conclusion, we found that circARHGAP12 exerted the oncogenic role in cervical cancer progression through m6A-dependent IGF2BP2/FOXM1 pathway. These findings may provide new concepts for cervical cancer biology and pathological physiology.