Abstract
BackgroundIt has been shown that circular RNAs (circRNAs) play a vital role in the progression of glioma. Recently, hsa_circ_0001836 was found to be upregulated in glioma tissues, but the role of hsa_circ_0001836 in glioma remains unclear.MethodsEdU staining and flow cytometry assays were used to measure the viability and death of glioma cells. In addition, scanning electron microscopy (SEM) was used to observe the morphology of cells undergoing cell death.ResultsHsa_circ_0001836 expression was upregulated in U251MG and SHG-44 cells. In addition, hsa_circ_0001836 knockdown significantly reduced the viability and proliferation of U251MG and SHG-44 cells. Moreover, hsa_circ_0001836 knockdown markedly induced the pyroptosis of U251MG and SHG-44 cells, evidenced by the increased expressions of NLRP1, cleaved caspase 1 and GSDMD-N. Meanwhile, methylation specific PCR (MSP) results indicated that hsa_circ_0001836 knockdown epigenetically increased NLRP1 expression via mediating DNA demethylation of NLRP1 promoter region. Furthermore, downregulation of hsa_circ_0001836 notably induced pyroptosis and inhibited tumor growth in a mouse xenograft model of glioma.ConclusionCollectively, hsa_circ_0001836 knockdown could induce pyroptosis cell death in glioma cells in vitro and in vivo via epigenetically upregulating NLRP1 expression. These findings suggested that hsa_circ_0001836 may serve as a potential therapeutic target for the treatment of glioma.
Highlights
Glioma is the most common form of intracranial neoplasm, characterizing by uncontrolledproliferation and unparalleled invasiveness [1,2,3,4]
Hsa_circ_0001836 knockdown significantly increased IL-1b and IL-18 secretion in U251MG cells (Figures 3E, F). These results suggested that hsa_circ_0001836 knockdown could trigger the pyroptosis in glioma cells via activation of NLRP1GSDMD signaling
We found that annexin+/PI+ cells, indicative of late apoptosis, necrosis and pyroptosis, were increased in hsa_circ_0001836 siRNA3 transfected cells
Summary
Glioma is the most common form of intracranial neoplasm, characterizing by uncontrolledproliferation and unparalleled invasiveness [1,2,3,4]. According to the World Health Organization (WHO) classification, gliomas can be categorized into grades I to IV based on malignancy and overall survival [5, 6]. Among all the subtypes of gliomas, glioblastoma (GBM, grade IV) is the most aggressive type of malignant gliomas [7]. Glioma is a common primary malignant brain tumor with high morbidity and mortality [8]. Advances have been made in the CircRNA hsa_circ_0001836 Regulates the Progression of Glioma treatment of gliomas, the overall survival time for patients with gliomas is less than 16 months after diagnosis [9, 10]. It has been shown that circular RNAs (circRNAs) play a vital role in the progression of glioma. Hsa_circ_0001836 was found to be upregulated in glioma tissues, but the role of hsa_circ_0001836 in glioma remains unclear
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