Pyroptosis is a type of proinflammatory programmed cell death mediated by caspase 1 activity and occurs in several types of eukaryotic tumor cells, including gliomas. MicroRNAs (miRNAs), small endogenous noncoding RNAs, have been demonstrated to be advantageous in glioma therapy. However, the question of whether miRNAs regulate pyroptosis in glioma remains unknown. The current study found that caspase 1 expression was substantially increased in both glioma tissues and glioma cell lines, U87 and T98G, while miR-214 expression was significantly downregulated. Luciferase reporter assay recognized caspase 1 as a target gene of miR-214. These findings demonstrate that miR-214 could inhibit cell proliferation and migration through the regulation of pyroptosis intermediated by caspase 1 in glioma U87 and T98G cells and may suggest a novel therapeutic for the intervention of glioma.
Our study for the first time demonstrated a significant correlation between HS ILAE types and long-term postoperative seizure outcome in patients with MTLE due to HS. Therefore, HS ILAE types have predictive value in long-term seizure outcome following epilepsy surgery.
Glioma-initiating cells (GIC) are glioma stem-like cells that contribute to glioblastoma (GBM) development, recurrence, and resistance to chemotherapy and radiotherapy. They have recently become the focus of novel treatment strategies. Cyclophilin A (CypA) is a cytosolic protein that belongs to the peptidyl-prolyl isomerase (PPIase) family and the major intracellular target of the immunosuppressive drug cyclosporin A (CsA). In this study, we investigate the functions of CypA and its mechanism of action in GICs' development. We analyzed differences in CypA expression between primary tumors and neurospheres from the GDS database, both before and after GIC differentiation. A series of experiments was conducted to investigate the role of CypA in GIC stemness, self-renewal, proliferation, radiotherapy resistance, and mechanism. We then designed glutathione S-transferase (GST) pulldown and coimmunoprecipitation assays to detect signaling activity. In this study, we demonstrated that CypA promotes GIC stemness, self-renewal, proliferation, and radiotherapy resistance. Mechanistically, we found that CypA binds β-catenin and is recruited to Wnt target gene promoters. By increasing the interaction between β-catenin and TCF4, CypA enhances transcriptional activity. Our results demonstrate that CypA enhances GIC stemness, self-renewal, and radioresistance through Wnt/β-catenin signaling. Due to its promotive effects on GICs, CypA is a potential target for future glioma therapy. .
Introduction: Glioma is one of the most common and most aggressive brain tumors in humans. The molecular and cellular mechanisms responsible for the onset and the progression of glioma are elusive and controversial. Centrosomal protein of 55 (CEP55) was initially described as a highly coiled-coil protein that plays critical roles in cell division, but was recently identified as being overexpressed in many human cancers. The function of CEP55 has not previously been characterized in glioma. We aim to discover the effect and mechanism of CEP55 in glioma development.Method: qRT-PCR and immunohistochemistry were used to analyze CEP55 expression. Glucose uptake, western blot, MTS, CCK-8, Caspase-3 activity and TUNEL staining assays were performed to investigate the role and mechanism of CEP55 on glioma cell process.Results: We found that the levels of CEP55 expression were upregulated in glioma. In addition, CEP55 appeared to regulate glucose metabolism of glioma cells. Furthermore, knockdown of CEP55 inhibited cell proliferation and induced cell apoptosis in glioma. Finally, we provided preliminary evidence that knockdown of CEP55 inhibited glioma development via suppressing the activity of Akt/mTOR signaling.Conclusions: Our results demonstrated that CEP55 regulates glucose metabolism, proliferation and apoptosis of glioma cells via the Akt/mTOR signaling pathway, and its promotive effect on glioma tumorigenesis can be a potential target for glioma therapy in the future.
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