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

Fei Ji, Yang Lu, Shaoyun Chen, Yu Yan, Xiaoling Lin, Yuanfang Zhu, Xin Luo

2021Cell Death Discovery83 citationsDOIOpen Access PDF

Abstract

Abstract Emerging evidence indicates that circular RNA (circRNA) and N 6 -methyladenosine (m 6 A) play critical roles in cervical cancer. However, the synergistic effect of circRNA and m 6 A on cervical cancer progression is unclear. In the present study, our sequencing data revealed that a novel m 6 A-modified circRNA (circARHGAP12, hsa_circ_0000231) upregulated in the cervical cancer tissue and cells. Interestingly, the m 6 A 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 m 6 A site in FOXM1 mRNA. CircARHGAP12 interacted with m 6 A 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 m 6 A-dependent IGF2BP2/FOXM1 pathway. These findings may provide new concepts for cervical cancer biology and pathological physiology.

Topics & Concepts

FOXM1Downregulation and upregulationCervical cancerCancer researchMessenger RNABiologyRNACircular RNATumor progressionCancerPathologicalCell biologyInternal medicineMedicineGeneGeneticsCircular RNAs in diseasesRNA modifications and cancerCancer-related molecular mechanisms research