A circular RNA derived from GLIS3 accelerates the proliferation of glioblastoma cells through competitively binding with miR-449c-5p to upregulate CAPG and GLIS3.

BACKGROUND: Glioblastoma (GBM) is an aggressive and malignant brain tumor with extremely poor prognosis. Despite advances in treatment, the pathogenesis of GBM remains elusive. Mounting studies have revealed the critical role of circular RNAs (circRNAs) in the development and progression of human cancers including GBM, but the comprehension of their functions is still insufficient. In this study, we investigated the expression profile of a circRNA derived from GLIS family zinc finger 3 (GLIS3) in GBM and normal astrocytes. CircGLIS3 expression was detected through quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Functional experiments were performed to analyze the influence of circGLIS3 on GBM cell proliferation and apoptosis. In addition, mechanism assays were to uncover the potential regulatory mechanism of circGLIS3. RESULTS: CircGLIS3 was up-regulated in GBM cells and knockdown of circGLIS3 significantly hampered proliferation and promoted apoptosis of GBM cells. Furthermore, circGLIS3 positively regulated CAPG and GLIS3 by sponging miR-449c-5p to affect GBM cell proliferation and apoptosis. CONCLUSIONS: In summary, our study identified that circGLIS3 could promote proliferation and inhibit apoptosis of GBM cells via targeting miR-449c-5p/GLIS3/CAPG axis in vitro. This study could offer a novel molecular perspective for further investigation into mechanisms essential to GBM progression.

Knockdown of circ_0055412 promotes cisplatin sensitivity of glioma cells through modulation of CAPG and Wnt/ß-catenin signaling pathway.

INTRODUCTION: Glioma is the most frequent primary cerebral tumor in adults. Recent evidence has suggested that circular RNAs (circRNAs) are associated with the pathological processes in glioma. In our study, we aimed to investigate the function and mechanism of circ_CAPG (circ_0055412) in glioma. METHODS: Firstly, circ_0055412 expression was examined through RT-qPCR analysis. Loss-of-function assays and animal experiments were implemented to evaluate the role of circ_0055412 on cisplatin resistance of glioma cells. Moreover, mechanism assays were done to probe into the regulatory mechanism of circ_0055412 in glioma cells. RESULTS: Circ_0055412 was found to be notably upregulated in glioma cells. Moreover, depletion of circ_0055412 enhanced cisplatin sensitivity of glioma cells in vitro and in vivo. Moreover, circ_0055412 recruited eukaryotic translation initiation factor 4A3 (EIF4A3) protein to stabilize capping actin protein, gelsolin like (CAPG) mRNA. Furthermore, circ_0055412 served as a sponge for microRNA-330-3p (miR-330-3p) and regulated nuclear factor of activated T cells 3 (NFATC3) expression to activate the transcription of catenin beta 1 (CTNNB1), thus participating in the activation of Wnt/ß-catenin signaling pathway. CONCLUSION: Circ_0055412 contributed to cisplatin resistance of glioma cells via stabilizing CAPG mRNA and modulating Wnt/ß-catenin signaling pathway. This finding might provide novel information for the treatment of glioma.

Analysis of clinical characteristics of macrophage capping protein (CAPG) gene expressed in glioma based on TCGA data and clinical experiments.

Macrophage capping protein (CAPG) genes were investigated based on The Cancer Genome Atlas (TCGA) database and clinical experiments. Glioblastoma (GBM) genes expression profiling chip of 529 disease samples and 10 normal samples selected from TCGA database were used for analysis, 25 brain glioma tissue samples and 15 normal brain tissues were collected in the Department of Neurosurgery of the First Affiliated Hospital of Xinjiang Medical University in China from 2016 to 2017 to analyze CAPG genes. TCGA results showed that the expression level of CAPG genes in GBM was higher than that in normal tissues, and the expression level of men, aged over 46 years and high grade gliomas in pathological stages was higher than that of women, aged ≤46 and low grade gliomas in pathological stages, and the survival time of high expression was shorter than that of low expression. The expression level of CAPG in glioma tissues was higher than that in normal tissues, and the expression level of CAPG in males was higher than that in females, as males had lymphatic transfer and low differentiation compared with females, but the expression level was not related to age. Survival analysis showed that higher expression level indicated shorter survival time, they were positively correlated. The expression of CAPG in glioma is high, and it is highly expressed with the severity of the disease, and it is also obviously related to the prognosis. Therefore, CAPG could be used as a biomarker for pathological grade and prognosis in glioma. However, the related studies are not consistent on the expression of different sex and ages, so further study is needed.