IGF2BP2 stabilized FBXL19-AS1 regulates the blood-tumour barrier permeability by negatively regulating ZNF765 by STAU1-mediated mRNA decay.
Xiaobai LiuPeiqi WuRui SuYixue XueChunqing YangDi WangXuelei RuanJian ZhengYang YangZhen LiYunhui LiuPublished in: RNA biology (2020)
Blood-tumour barrier (BTB) has been known to significantly attenuate the efficacy of chemotherapy for glioma. In this report, we identified that insulin-like grown factor 2 mRNA-binding protein 2 (IGF2BP2) was over-expressed in glioma microvessel and glioma endothelial cells (GECs). Knockdown of IGF2BP2 decreased the expression of lncRNA FBXL19-AS1 and tight junction-related proteins, thereby promoting BTB permeability. FBXL19-AS1 was over-expressed and more enriched in the cytoplasm of GECs. In addition, FBXL19-AS1 could bind to 3'-UTR of ZNF765 mRNA and down-regulate ZNF765 mRNA expression through STAU1-mediated mRNA decay (SMD). The low expression of ZNF765 was discovered in GECs and verified to increase BTB permeability by inhibiting the promoter activities of tight junction-related proteins. Meanwhile, ZNF765 also inhibited the transcriptional activity of IGF2BP2, thereby forming a feedback loop in regulating the BTB permeability. Single or combined application of silenced IGF2BP2 and FBXL19-AS1 improved the delivery and antitumor efficiency of doxorubicin (DOX). In general, our study revealed the regulation mechanism of IGF2BP2/FBXL19-AS1/ZNF765 axis on BTB permeability, which may provide valuable insight into treatment strategy for glioma.
Keyphrases
- binding protein
- endothelial cells
- transcription factor
- blood brain barrier
- type diabetes
- dna methylation
- poor prognosis
- growth hormone
- high glucose
- pi k akt
- drug delivery
- single cell
- signaling pathway
- insulin resistance
- oxidative stress
- rectal cancer
- weight loss
- combination therapy
- heat shock protein
- heat shock
- long noncoding rna
- heat stress
- smoking cessation
- drug induced