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RBFOX1 Regulates the Permeability of the Blood-Tumor Barrier via the LINC00673/MAFF Pathway
- Source :
- Molecular Therapy: Oncolytics, Vol 17, Iss , Pp 138-152 (2020)
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- The blood-tumor barrier limits the delivery of therapeutic drugs to brain tumor tissues. Selectively opening the blood-tumor barrier is considered crucial for effective chemotherapy of glioma. RNA-binding proteins have emerged as crucial regulators in various biologic processes. This study found that RNA-binding Fox-1 homolog 1 (RBFOX1) was downregulated in glioma vascular endothelial cells derived from glioma tissues, and in glioma endothelial cells obtained by co-culturing endothelial cells with glioma cells. Overexpression of RBFOX1 impaired the integrity of the blood-tumor barrier and increased its permeability. Additionally, RBFOX1 overexpression decreased the expression of tight junction proteins ZO-1, occludin, and claudin-5. Subsequent analysis of the mechanism indicated that the overexpression of RBFOX1 increased musculoaponeurotic fibrosarcoma protein basic leucine zipper [bZIP] transcription factor F (MAFF) expression by downregulating LINC00673, which stabilized MAFF messenger RNA (mRNA) through Staufen1-mediated mRNA decay. Moreover, MAFF could bind to the promoter region and inhibit the promoter activities of ZO-1, occludin, and claudin-5, which reduced its expression. The combination of RBFOX1 upregulation and LINC00673 downregulation promoted doxorubicin delivery across the blood-tumor barrier, resulting in apoptosis of glioma cells. In conclusion, this study indicated that overexpression of RBFOX1 increased blood-tumor barrier permeability through the LINC00673/MAFF pathway, which might provide a new useful target for future enhancement of blood-tumor barrier permeability.
Details
- Language :
- English
- ISSN :
- 23727705
- Volume :
- 17
- Issue :
- 138-152
- Database :
- Directory of Open Access Journals
- Journal :
- Molecular Therapy: Oncolytics
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.8784d8b09b2147e3bc139fdcc0fa59a3
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.omto.2020.03.014