CircPIK3C2A Facilitates the Progression of Glioblastoma via Targeting miR-877-5p/FOXM1 Axis

Jian Yang; Shuaiwei Tian; Baocheng Wang; Jiajia Wang; Liangliang Cao; Qinhua Wang; Wanqun Xie; Zhuangzhuang Liang; Heng Zhao; Yang Zhao; Keman Liao; Jie Ma

doi:10.3389/fonc.2021.801776

CircPIK3C2A Facilitates the Progression of Glioblastoma via Targeting miR-877-5p/FOXM1 Axis

Front Oncol. 2021 Dec 24:11:801776. doi: 10.3389/fonc.2021.801776. eCollection 2021.

Authors

Jian Yang¹, Shuaiwei Tian¹, Baocheng Wang¹, Jiajia Wang¹, Liangliang Cao¹, Qinhua Wang¹, Wanqun Xie¹, Zhuangzhuang Liang¹, Heng Zhao¹, Yang Zhao¹, Keman Liao^{2

3}, Jie Ma¹

Affiliations

¹ Department of Pediatric Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Brain Injury Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
³ Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Abstract

Glioblastoma is a rare yet lethal type of tumor that poses a crucible for the medical profession, owing to its rapid proliferation and invasion resulting in poor prognosis. Circular RNAs (circRNAs), a subclass of regulatory RNAs, are implicated in the regulation of cancerous progression. This study aims to investigate the roles and underlying mechanism of circPIK3C2A in regulating proliferation and invasion of glioblastoma. qRT-PCR assays showed that the expression level of circPIK3C2A was aberrantly higher in glioblastoma cell lines, in comparison with that in normal glia cells. The ectopic expression of circPIK3C2A promoted the proliferation, invasion and clonal formation of glioblastoma cells, while circPIK3C2A loss-of-function exerted exactly the opposite biological effects on the cells. The construction of subcutaneous xenograft tumor model in nude mice indicated that circPIK3C2A loss-of-function effectively diminished tumor load in vivo and prolonged the survival time of tumor-bearing animals. Luciferase reporter assay confirmed the interaction among circPIK3C2A/miR-877-5p and FOXM1. CircPIK3C2A function as competitive endogenous RNA via sponging miR-877-5p through certain binding sites, thereby modulating the expression of FOXM1. Our results collectively indicate that circPIK3C2A functions as ceRNA by mediating miR-877-5p/FOXM1 axis, providing a novel perspective of applying CircPIK3C2A in the clinical intervention of glioblastoma in the future.

Keywords: CircPIK3C2A; FOXM1; competing endogenous RNA (CeRNA); glioblastoma; miR-877-5p.