OBJECTIVE: The present study aimed to explore the expression profiles of circular RNAs (circRNAs) in glioblastoma multiforme (GBM) in an attempt to identify potential core genes in the pathogenesis of this tumor. METHODS: Differentially expressed circRNAs were screened between tumor tissues from five GBM patients and five normal brain samples using Illumina Hiseq. Bioinformatics analysis was used to analyze their potential function. CircBRAF was further detected in different WHO grades glioma tissues and normal brain tissues. Kaplan-Meier curves and multivariate Cox's analysis were used to analyze the association between circBRAF expression level and prognosis of glioma patients. RESULTS: A total of 1411 differentially expressed circRNAs were identified in GBM patients including 206 upregulated circRNAs and 1205 downregulated circRNAs. Differential expression of circRNAs was closely associated with the biological process and molecular function. The downregulated circRNAs were mainly associated with ErbB and Neurotrophin signaling pathways. Moreover, the expression level of circBRAF in normal brain tissues was significantly higher than that in glioma tissues (P < .001). CircBRAF was significantly lower in glioma patients with high pathological grade (WHO III & IV) than those with low grade (WHO I & II) (P < .001). Cox analysis revealed that high circBRAF expression was an independent biomarker for predicting good progression-free survival and overall survival in glioma patients (HR = 0.413, 95% CI 0.201-0.849; HR = 0.299, 95% CI 0.135-0.661; respectively). CONCLUSION: The present study identified a profile of dysregulated circRNAs in GBM. Bioinformatics analysis showed that dysregulated circRNAs might be associated with tumorigenesis and development of GBM. In addition, circBRAF could severe as a biomarker for predicting pathological grade and prognosis in glioma patients.

Brain glioma is the most common malignant tumor of the central nervous system, and one of the leading causes of death in patients with intracranial tumors. The clinical outcome of glioma is usually poor due to abundant vascularity, fast growth and susceptibility of invasion to normal brain tissues. Our microarray study showed that lncRNA‐LINC01116 was significantly upregulated in glioma tissues and played an important role in cell proliferation, cycle, migration, invasion and angiogenesis. In addition, vascular endothelial growth factor (VEGFA) may be the major target genes in the downstream of lncRNA‐LINC01116. Dual luciferase assay showed that LINC01116 and VEGFA both contained a miR‐31‐5p binding site, and LINC01116 could regulate the expression of VEGFA through competitive absorption of miR‐31‐5p. RNA immunoprecipitation indicated that LINC01116 and VEGFA were present in the miR‐31‐5p‐RISC complex, and biotinylated miR‐31‐5p pull‐down assay suggested that there was a competitive relationship between LINC01116 and VEGFA to bind with miR‐31‐5p. Collectively, our study has identified a novel lncRNA‐LINC01116 and clarified the role and mechanism of LINC01116 in the tumorigenesis of glioma. LINC01116 may prove to be a potential target for the clinical diagnosis and treatment of glioma.

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Spinal World Health Organization (WHO) II and III meningiomas are relatively rare, and often associated with great clinical aggressiveness and poor overall survival. There are controversies over factors affecting the prognosis of this disease. The aim of this retrospective study was to evaluate factors that may affect the therapeutic outcome and prognosis of adult high-grade spinal meningiomas by reviewing the medical records of 25 patients who were surgically treated in our hospital between 2001 and 2014. Univariate and multivariate analyses were performed to identify prognostic variables relative to patient and tumor characteristics, and treatment modalities. All 25 patients (14 men and 11 women; mean age 46.6 ± 16.1 years) underwent surgical resection. Local recurrence was occurred in 13 (52.0 %) patients, and 10 (40.0 %) patients died during the follow-up periods. The 5-year recurrence rate was 60.0 % and the 5-year survival rate was 68.0 %. The results of statistical analysis suggested that Simpson resection grade and the number of involved segments were prognostic factors related to progression-free survival and that sex, age, preoperative Frankel score, the number of involved segments and WHO grade were closely correlated with survival. Furthermore, we confirmed that the number of involved segments was the major independent factor affecting recurrence of patients with adult spinal high-grade meningiomas, and that sex, age and WHO grade were prognostic factors affecting survival but not recurrence.

Although intracranial ependymoma is relatively rare, it is often associated with great clinical aggressiveness and poor overall survival. There are controversies over factors affecting the prognosis of the disease. The aim of this retrospective study was to evaluate factors that may affect the therapeutic outcome and prognosis of intracranial ependymoma by reviewing the medical records of 49 patients who were surgically treated in our hospital between 2001 and 2014. Univariate and multivariate analyses were performed to identify prognostic variables relative to patient and tumor characteristics, and treatment modalities. All 49 patients (24 men and 25 women; mean age 27.6 years) underwent surgical resection, of whom 14 patients also underwent postoperative radiotherapy. Local recurrence was found in 15 (48.8 %) patients, and 22 (51.2 %) patients died during the follow-up periods. The 5-year recurrence rate was 65 % and the survival rate was 51 %. The results of statistical analysis suggested that preoperative extraventricular drainage and surgical resection extent were prognostic factors related to progression-free survival, and that age, surgical resection extent and histological grade were closely associated with survival. Interestingly, there was a significant correlation between the symptom of hydrocephalus and age (P = 0.010), and patients with a better clinical status (KPS ≥ 80) were significantly associated with a lower WHO grade (P = 0.007). In conclusion, we confirmed that surgical resection extent was the major independent factor affecting both recurrence and survival of patients with intracranial ependymoma, while age and WHO grade were prognostic factors affecting survival but not recurrence.

Purpose: The pathogenesis of glioma is not clear, SALL4 is a protooncogene and has been shown to promote the growth of glioma cells. CircRNAs have been shown to play a role in the development of tumors, but the relationship between SALL4 and circRNAs has not been well characterized. The aim of this study is to establish the association between SALL4 and circRNAs.Methods: The circRNAs and miRNAs related to SALL4 screened before were detected in glioma and normal brain tissue samples, then hsa_circ_0024183 was selected to determine its effect on glioma progression in vivo and vitro. The interaction between hsa_circ_0024183, miR-485-5p and SALL4 was clarified by double luciferase assay and RNA immunoprecipitation analysis.Results: The expression of hsa_circ_0024183 was significantly higher in glioma patients and human glioblastoma cell lines than in normal brain(P<0.05). GBM patients with higher hsa_circ_0024183 expression had worse outcome. The reduction of hsa_circ_0024183 by siRNA was found to decrease the proliferation, migration, and invasion abilities of GBM cells and block their cell cycles at the S phase. Furthermore, a decrease of hsa_circ_0024183 expression in GBM cells was found to inhibit their tumorigenicity in nude mice. Mechanistic studies revealed that hsa_circ_0024183 can regulate SALL4 expression by sponging miR-485-5p. And hsa_circ_0024183 RNA could directly bind to SALL4 protein.Conclusion: Interference with hsa_circ_0024183 can reduce the expression of SALL4 and the binding of hsa_circ_0024183 to SALL4 protein. It may affect the progression of glioma through the PTEN/PI3K/Akt pathway. This discovery provides an opportunity to develop potential targeted therapy against glioma.

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