Abstract
BackgroundGlioblastoma (GBM) is characterized by progressive growth and metastasis. Numerous studies claim that the deregulation of circular RNAs (circRNAs) is associated with cancer progression. However, the role of circRNAs in GBM is largely limited. The purpose of this study was to investigate the functions of circCDC45 in GBM and provide a feasible functional mechanism to support its role.MethodsThe expression of circCDC45, miR-485-5p and colony-stimulating factor 1 (CSF-1) mRNA was examined using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed using cell counting kit − 8 (CCK-8) assay and colony formation assay. Cell migration and cell invasion were monitored using transwell assay. The protein levels of proliferation-related markers and CSF-1 were determined using western blot. The target relationship was predicted using bioinformatics tools and validated using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Animal models were constructed to verify the role of circCDC45 in vivo.ResultsThe expression of circCDC45 and CSF-1 was elevated in GBM tissues and cells, while the expression of miR-485-5p was declined. Downregulation of circCDC45 or CSF-1 blocked GBM cell proliferation, invasion and migration as well as tumor growth in vivo. In mechanism, circCDC45 positively regulated the expression of CSF-1 by targeting miR-485-5p. Inhibition of miR-485-5p reversed the biological effects caused by circCDC45 downregulation in GBM cells.ConclusionCircCDC45 promoted the progression of GBM by mediating the miR-485-5p/CSF-1 axis, and circCDC45 might be a promising plasmatic biomarker for GBM diagnosis and treatment.
Highlights
Glioblastoma (GBM) is characterized by progressive growth and metastasis
A total of 18 miRNAs targeted by circCDC45 were obtained from starBase, and a total of 35 miRNAs targeted by circCDC45 were obtained from circbank, including 6 miRNAs in both starBase and circbank (Fig. 3A). We focused on these 6 miRNAs and examined their expression in LN229 and A172 cells with circCDC45 overexpression
The mutant sequence of colony-stimulating factor 1 (CSF-1) 3′ untranslated regions (3’UTR) and the wild sequence of CSF-1 3’UTR were amplified and cloned into luciferase reporter plasmid, and we found miR-485-5p restoration strikingly reduced the luciferase activity of LN229 and A172 cells transfected with CSF-1 3’UTR-WT (Fig. 5B and C)
Summary
Glioblastoma (GBM) is characterized by progressive growth and metastasis. Numerous studies claim that the deregulation of circular RNAs (circRNAs) is associated with cancer progression. The role of circRNAs in GBM is largely limited. The purpose of this study was to investigate the functions of circCDC45 in GBM and provide a feasible functional mechanism to support its role. Glioblastoma (GBM) is one of the common primary brain tumors [1]. The median survival time of GBM patients is only about 14.6 months, and almost all patients have a poor prognosis [2]. GBM cells infiltrating into nearby brain tissues can cause tumor recurrence [3, 5]. GBM is considered to be one of the most aggressive and most difficult cancers to treat [6]. The identification and verification of prognosis and predictive biomarkers are of great significance for the understanding of tumor molecular characteristics and targeted therapy
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