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

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

doi:10.1038/s41420-021-00595-w

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.

Highlights

Cervical cancer is the second most frequent malignant cancer for women worldwide and the third primary cause of cancer-related death in developing countries [1, 2]
Our research found that circARHGAP12 could enhance the stability of FOXM1 mRNA via binding with IGF2BP2
RESULTS circARHGAP12 was an unfavorable circRNA for cervical cancer Using the circRNA microarray analysis, we found that there were hundreds of circRNAs varied within the cervical cancer tissue and adjacent normal tissue (Fig. 1A, B)

Summary

Introduction

Cervical cancer is the second most frequent malignant cancer for women worldwide and the third primary cause of cancer-related death in developing countries [1, 2]. The increasing application of cervical smear screening and the cervical cancer vaccine make the mortality and morbidity of cervical cancer decreasing, the molecular mechanism underlying cervical cancer is not entirely explicit [3]. Upregulated circRNA hsa_circRNA_101996 serves as a miR-8075 sponge to target TPX2 in cervical cancer, thereby promoting cervical cancer proliferation and invasion [9]. These data suggests that circRNA might function as an oncogenic or anticancer element

Methods

Results

Conclusion