Biosynthetic CircRNA_001160 induced by PTBP1 regulates the permeability of BTB via the CircRNA_001160/miR-195-5p/ETV1 axis

Cell Death Dis. 2019 Dec 20;10(12):960. doi: 10.1038/s41419-019-2191-z.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Capillary Permeability / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Central Nervous System / drug effects
  • Central Nervous System / pathology
  • DNA-Binding Proteins / genetics*
  • Doxorubicin / pharmacology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioma / drug therapy
  • Glioma / genetics*
  • Glioma / pathology
  • Heterogeneous-Nuclear Ribonucleoproteins / genetics*
  • Humans
  • MicroRNAs / genetics*
  • Polypyrimidine Tract-Binding Protein / genetics*
  • Promoter Regions, Genetic / genetics
  • RNA, Circular / genetics*
  • Transcription Factors / genetics*

Substances

  • DNA-Binding Proteins
  • ETV1 protein, human
  • Heterogeneous-Nuclear Ribonucleoproteins
  • MIRN195 microRNA, human
  • MicroRNAs
  • PTBP1 protein, human
  • RNA, Circular
  • Transcription Factors
  • Polypyrimidine Tract-Binding Protein
  • Doxorubicin