Abstract
The presence of the blood-tumor barrier (BTB) severely impedes the transport of anti-neoplasm drugs to the central nervous system, affecting the therapeutic effects of glioma. Glioma endothelial cells (GECs) are the main structural basis of the BTB. Circular RNA is considered to be an important regulator of endothelial cell growth. In this study, we found that polypyrimidine tract binding protein 1 (PTBP1) and circRNA_001160 were remarkably upregulated in GECs. Knockdown of PTBP1 or circRNA_001160 significantly increased BTB permeability, respectively. As a molecular sponge of miR-195-5p, circRNA_001160 attenuated its negative regulation of the target gene ETV1 by adsorbing miR-195-5p. In addition, ETV1 was overexpression in GECs. ETV1 bounded to the promoter regions of tight junction-related proteins and increased the promoter activities, which significantly promoted the expression levels of tight junction-related proteins. The present study showed that the combined application of PTBP1, circRNA_001160, and miR-195-5p with the anti-tumor drug Dox effectively promoted Dox through BTB and extremely induced the apoptosis of glioma cells. Our results demonstrated that the PTBP1/circRNA_001160/miR-195-5p/ETV1 axis was critical in the regulation of BTB permeability and provided new targets for the treatment of glioma.
Highlights
Glioblastoma (GBM) is the most common primary malignant brain tumor in the adult central nervous system with its highly invasiveness and diffusivity[1]
polypyrimidine tract binding protein 1 (PTBP1) was upregulated in Glioma endothelial cells (GECs), and knockdown of PTBP1 increased blood-tumor barrier (BTB) permeability QRT-PCR and western blot were used to detect the expression of PTBP1
There was no significant difference between the knockdown of PTBP1 negative control group and the control group
Summary
Glioblastoma (GBM) is the most common primary malignant brain tumor in the adult central nervous system with its highly invasiveness and diffusivity[1]. Despite the use of most conventional therapies such as surgical resection and chemoradiotherapy, patients with glioma still gain poor postoperative outcomes, high recurrence rates, and low survival rates[2]. The blood-tumor barrier (BBB) is composed of normal capillary endothelial cells (ECs), preventing the entry of harmful substances, and is an indispensable vascular barrier to protect the brain[3,4]. Glioma leads to the BBB structure remodeling, forming the blood-tumor barrier (BTB)[5]. The BTB constitutes major obstacles to the transport of therapeutics in brain tumors[6]. Selective opening of the BTB to increase antineoplasm drugs concentration in tumor tissues is crucial for the treatment of malignant glioma
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