Circular RNA Complement Factor H (CFH) Promotes Glioma Progression by Sponging miR-149 and Regulating AKT1.

BACKGROUND Circular RNAs (circRNAs) are widely expressed in mammals and can regulate the development and progression of human tumors. has_circ_0015758 (circ-CFH) is an exon circRNA transcript from the GRCh37/hg19 fragment of chromosome 1 and is homologous to the protein-coding gene complement factor H (CFH). Currently, the function of circ-CFH in glioma remains unclear. MATERIAL AND METHODS In our study, circ-CFH, miR-149, and Akt1 mRNA expression levels were analyzed by qRT-PCR assays. To investigate the function of circ-CFH in cell proliferation, circ-CFH knockdown models were established by using circ-CFH siRNAs. Cell proliferation abilities were measured by CCK-8 and colony formation assays and in vivo experiments. In addition, the interaction between circ-CFH and miR-149 was assessed by luciferase reporter assays. RESULTS Circ-CFH expression was significantly upregulated in glioma tissue and was correlated with tumor grade. Circ-CFH expression levels were also markedly higher in U251 and U373 glioma cell lines. Circ-CFH knockdown inhibited cell proliferation and colony formation abilities. Luciferase assays indicated that circ-CFH functions as a miR-149 sponge and inhibits its function in U251 and U373 cells. Subsequently, AKT1 was identified as a direct target of the circ-CFH/miR-149 axis. CONCLUSIONS Circ-CFH promotes glioma progression by sponging miR-149 and regulating the AKT1 signaling pathway. The circ-CFH/miR-149/AKT1 regulation axis may be a potential target for glioma therapy.

Tumor microRNA-335 expression is associated with poor prognosis in human glioma.

MicroRNA-335 (miR-335), as a transcript of genomic region chromosome 7q32.2, acts as a tumor suppressor or tumor promoter in various human malignancies. Especially, it has been reportedly shown to be an oncogene in human glioma cell line in vitro, but its expression in human glioma tissues is not yet determined. The aim of this study was to investigate the clinical significance of miR-335 expression in glioma. MiR-335 expression in human gliomas and nonneoplastic brain tissues was measured by real-time quantitative RT-PCR assay. The association of miR-335 expression with clinicopathological factors and prognosis of glioma patients was statistically analyzed. The expression level of miR-335 in glioma tissues was significantly higher than that in corresponding nonneoplastic brain tissues (P < 0.001). In addition, high miR-335 expression was significantly associated with a higher WHO grade (P = 0.001). Survival analysis demonstrated that patients with high miR-335 expression tumors had significantly shorter survival times than those with low miR-335 expression tumors (P = 0.01) and that miR-335 was an independent prognostic factor (P = 0.02). Especially, subgroup analyses according to tumor histologic grade revealed that the mean survival time of patients with high grade (III-IV) was significantly worse for high miR-335 expression group than for low miR-335 expression group (P = 0.002), but no significant difference was found for patients with WHO grade I-II (P = 0.16). These results indicated that miR-335 expression was increased in human gliomas and was associated with advanced tumor progression. Furthermore, miR-335 expression was demonstrated for the first time to be an independent marker for predicting the clinical outcome of patients with gliomas.

Wnt/beta-Catenin pathway in human glioma: expression pattern and clinical/prognostic correlations.

Gliomas are the most common primary intracranial tumors. Understanding the molecular basis of gliomas' progression is required to develop more effective therapies. The Wnt/ß-catenin signaling cascade is an important signal transduction pathway in human cancers. Although, overactivation of this pathway is a hallmark of several forms of cancer, little is known about its role in human gliomas. Here, we aimed to determine the clinical significance of Wnt/ß-catenin pathway components in gliomas. Immunohistochemical staining was performed to detect the expression patterns of Wnt1, ß-catenin and Cyclin D1 in the biopsies from 96 patients with primary gliomas. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients. Cytoplasmic staining pattern of Wnt1, membranous, cytoplasmic and nuclear accumulation of ß-catenin, and nuclear localization of Cyclin D1 were demonstrated by immunohistochemical staining. The Wnt1 expression significantly correlated with the expression of Cyclin D1 (P < 0.0001). The ratio of tumors with a cytoplasmic-nuclear pattern or a cytoplasmic pattern of ß-catenin was significantly higher in Wnt1-positive (P < 0.01) and Cyclin D1-positive (P < 0.01) tumors than in Wnt1-negative and Cyclin D1-negative tumors, respectively. The protein expression levels of Wnt1, ß-catenin and Cyclin D1 were all positively correlated with the Karnofsky performance scale (KPS) score and World Health Organization (WHO) grades of patients with gliomas. Furthermore, Wnt1, cytoplasmic-nuclear ß-catenin and Cyclin D1 status were all the independent prognostic factors for glioma patients (P = 0.01, 0.007 and 0.005, respectively). These results provide convincing evidence that the Wnt/ß-catenin pathway correlated closely with the progression of gliomas and might be a novel prognostic marker for this neoplasm.