CircPITX1 Regulates Proliferation, Angiogenesis, Migration, Invasion, and Cell Cycle of Human Glioblastoma Cells by Targeting miR-584-5p/KPNB1 Axis.

Recent researches reported that several circular RNAs (circRNAs) were associated with the glioblastoma (GBM) progression, while the regulatory role of circPITX1 remains unknown in GBM. The real-time quantitative polymerase chain reaction (RT-qPCR) was used to quantify circPITX1, miR-584-5p, and karyopherin b1 (KPNB1) expression in GBM tissues and cells. The proliferation capability of cells was analyzed by Cell Counting Kit-8 (CCK-8) and colony-forming assays. The matrigel angiogenesis assay was used to assess tube formation in GBM cells. Flow cytometry assays were conducted to evaluate the cell cycle distribution of GBM cells. The migration and invasion assays were assessed by transwell assay. The Western blot assay was employed to quantify the protein expression level in GBM tissues and cells. The targets of circPITX1 and miR-584-5p were confirmed by dual-luciferase reporter and RNA pull-down assays. A xenograft experiment in nude mice was used to assess the functional role of circPITX1 in vivo. CircPITX1 was obviously overexpressed in GBM tissues and cells when compared with negative groups. The functional experiment implied that knockdown of circPITX1 suppressed proliferation, angiogenesis, migration, invasion, and tumor growth in vivo along with induced cell cycle arrest of GBM cells. Furthermore, miR-584-5p was a target gene of circPITX1, and knockdown of miR-584-5p could abolish circPITX1 silencing-induced effects on GBM cells. KPNB1 was a target gene of miR-584-5p, and functional experiments revealed that overexpression of miR-584-5p repressed proliferation, angiogenesis, migration, invasion, and cell cycle process in GBM cells by targeting KPNB1. Mechanistically, circPITX1/miR-584-5p/KPNB1 axis regulated GBM process via mediating proliferation, angiogenesis, migration, invasion, and cell cycle process of GBM cells.

Cao Y ，Wang F ，Chen Y ，Wang Y ，Song H ，Long J ... -  《-》

CircCDC45 promotes the malignant progression of glioblastoma by modulating the miR-485-5p/CSF-1 axis.

Glioblastoma (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. The 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. The 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. CircCDC45 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.

Liu R ，Dai W ，Wu A ，Li Y ... -  《BMC CANCER》

Blocking hsa_circ_0006168 suppresses cell proliferation and motility of human glioblastoma cells by regulating hsa_circ_0006168/miR-628-5p/IGF1R ceRNA axis.

Wang T ，Mao P ，Feng Y ，Cui B ，Zhang B ，Chen C ，Xu M ，Gao K ... -  《-》

Circ-0001801 contributes to cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT) in glioblastoma by regulating miR-628-5p/HMGB3 axis.

Chen WL ，Jiang L ，Wang JS ，Liao CX ... -  《-》

Circ_0005015 upregulates BACH1 to promote aggressive behaviors in glioblastoma by sponging microRNA-382-5p.

To investigate the potential role and molecular mechanism of circ_0005015 in GBM progression. Circ_0005015, microRNA-382-5p (miR-382-5p), and BTB domain and CNC homolog 1 (BACH1) levels were measured by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was determined by MTT, colony formation, and EdU assays. Cell apoptosis was analyzed using flow cytometry. Cell migration and invasion were assessed using wound healing and transwell assays. Glucose accumulation and lactate levels were examined by the corresponding kit. RNA pull-down and dual-luciferase reporter assays were performed to confirm the interaction between miR-382-5p and circ_0005015 or BACH1. Protein levels of MMP9, PCNA, and BACH1 were examined using western blot assay. Role of circ_0005015 on tumor growth in vivo was analyzed using a xenograft tumor model. Circ_0005015 content was up-regulated in GBM patients and cells, its knockdown restrained GBM cell proliferation, migration, invasion, glycolysis, and triggered apoptosis. Mechanistically, we found that circ_0005015 could directly interact with miR-382-5p and serve as a miRNA sponge to regulate BACH1 expression. In addition, circ_0005015 knockdown might repress tumor growth in vivo. Circ_0005015 boosted GBM progression via binding to miR-382-5p to up-regulate BACH1, which may offer new effective targets for GBM treatment.

Shao Y ，Yang Z ，Miao W ，Yu X ，Pu Y ... -  《-》