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

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

doi:10.1038/s41420-021-00595-w

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

Cell Death Discov. 2021 Aug 14;7(1):215. doi: 10.1038/s41420-021-00595-w.

Authors

Fei Ji^#^{1

2}, Yang Lu^#¹, Shaoyun Chen³, Yan Yu¹, Xiaoling Lin⁴, Yuanfang Zhu⁵, Xin Luo^{6

7}

Affiliations

¹ Department of Obstetrics and Gynecology, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen, 518102, China.
² The First Clinical Medical College of Jinan University, Guangzhou, 510632, China.
³ Maternal-Fetal Medicine Institute, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen, 518102, China.
⁴ Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, China.
⁵ Department of Obstetrics and Gynecology, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen, 518102, China. zhuyfdoctor@sina.com.
⁶ The First Clinical Medical College of Jinan University, Guangzhou, 510632, China. doctor_luoxin.edu@aliyun.com.
⁷ Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, China. doctor_luoxin.edu@aliyun.com.

^# Contributed equally.

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.