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

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.

Single‐cell RNA sequencing reveals SERPINE1‐expressing CAFs remodelling tumour microenvironment in recurrent osteosarcoma

“…SERPINE1 has been widely known to regulate the progression of numerous cancers, which highlights the application of SERPINE1 as a potential target. 9,10 We validated that SERPINE1 was remarkably correlated with macrophage infiltrations and the EMT of OS. Knocking down SERPINE1 by si-SERPINE1 could decrease CAFs infiltration and activity, and inhibit OS progression via inducing M1 macrophage polarisation (Figure 4).…”

MicorRNA-195 links long non-coding RNA SEMA3B antisense RNA 1 (head to head) and cyclin D1 to regulate the proliferation of glioblastoma cells

“…In conclusion, SEMA3B-AS1 is downregulated in GBM and overexpression of SEMA3B-AS1 can downregulate cyclin D1 and suppress GBM cell proliferation possibly through miR-195. With the increased understanding of the molecular mechanism of GBM [ 26 , 27 ], lncRNAs are expected to be targeted to treat GBM.…”

Posttranscriptional Regulation of the Plasminogen Activation System by Non-Coding RNA in Cancer

“…In glioblastoma (GBM) tissues, increased ZNF652 circRNA and PAI-1 and downregulation of miR-486 are associated with a poor prognosis. Indeed, ZNF652 upregulates PAI-1 expression in GBM cells by sponging miR-486, suggesting that targeting the ZNF652 circRNA may represent a novel and effective strategy to suppress cancer progression in GBM [ 61 ].…”