Identification of a novel circular RNA circZNF652/miR-486-5p/SERPINE1 signaling cascade that regulates cancer aggressiveness in glioblastoma (GBM)

鉴定出一种新型环状 RNA circZNF652/miR-486-5p/SERPINE1 信号级联,其可调节胶质母细胞瘤 (GBM) 中的癌症侵袭性

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作者:Liang Liu, Shan Xiao, Yan Wang, Zifeng Zhu, Yiyao Cao, Sen Yang, Rongkang Mai, Yong Zheng

Abstract

Circular RNAs (circRNAs) are closely associated with cancer development in glioblastoma (GBM), and this study aims to explore the molecular mechanisms of a novel circular RNA circZNF652 in regulating GBM aggressiveness. The present study found that CircZNF652 and SERPINE1 were upregulated, while miR-486-5p was downregulated in GBM tissues and cell lines, and GBM patients with high expression of CircZNF652 and SERPINE1, and patients with low expression of miR-486-5p tended to have a worse prognosis. Further results validated that both silencing of circZNF652 and miR-486-5p overexpression suppressed cell growth, migration, invasion, epithelial-mesenchymal transition (EMT) and tumorigenesis in GBM cells in vitro and in vivo. Next, the underlying mechanisms were investigated, and we found that circZNF652 sponged miR-486-5p to upregulate SERPINE1 in GBM cells. Also, we validated that knock-down of circZNF652 regulated the miR-486-5p/SERPINE1 axis to reverse the malignant phenotypes in GBM cells. Interestingly, we noticed that GBM cells derived exosomes were characterized by high-expressed CircZNF652. Collectively, we concluded that targeting the circular RNA circZNF652/miR-486-5p/SERPINE1 axis was a novel and effective strategy to suppress cancer progression in GBM.

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