RBFOX1 Regulates the Permeability of the Blood-Tumor Barrier via the LINC00673/MAFF Pathway

Shuyuan Shen; Chunqing Yang; Xiaobai Liu; Jian Zheng; Yunhui Liu; Libo Liu; Jun Ma; Teng Ma; Ping An; Yang Lin; Heng Cai; Di Wang; Zhen Li; Lini Zhao; Yixue Xue

Molecular Therapy: Oncolytics (Jun 2020)

RBFOX1 Regulates the Permeability of the Blood-Tumor Barrier via the LINC00673/MAFF Pathway

Shuyuan Shen,
Chunqing Yang,
Xiaobai Liu,
Jian Zheng,
Yunhui Liu,
Libo Liu,
Jun Ma,
Teng Ma,
Ping An,
Yang Lin,
Heng Cai,
Di Wang,
Zhen Li,
Lini Zhao,
Yixue Xue

Affiliations

Shuyuan Shen: Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang 110122, People’s Republic of China; Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang 110122, People’s Republic of China; Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang 110122, People’s Republic of China
Chunqing Yang: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of China; Liaoning Clinical Medical Research Center in Nervous System Disease, Shenyang 110004, People’s Republic of China; Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang 110004, People’s Republic of China
Xiaobai Liu: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of China; Liaoning Clinical Medical Research Center in Nervous System Disease, Shenyang 110004, People’s Republic of China; Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang 110004, People’s Republic of China
Jian Zheng: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of China; Liaoning Clinical Medical Research Center in Nervous System Disease, Shenyang 110004, People’s Republic of China; Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang 110004, People’s Republic of China
Yunhui Liu: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of China; Liaoning Clinical Medical Research Center in Nervous System Disease, Shenyang 110004, People’s Republic of China; Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang 110004, People’s Republic of China
Libo Liu: Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang 110122, People’s Republic of China; Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang 110122, People’s Republic of China; Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang 110122, People’s Republic of China
Jun Ma: Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang 110122, People’s Republic of China; Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang 110122, People’s Republic of China; Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang 110122, People’s Republic of China
Teng Ma: Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang 110122, People’s Republic of China; Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang 110122, People’s Republic of China; Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang 110122, People’s Republic of China
Ping An: Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang 110122, People’s Republic of China; Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang 110122, People’s Republic of China; Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang 110122, People’s Republic of China
Yang Lin: Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang 110122, People’s Republic of China; Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang 110122, People’s Republic of China; Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang 110122, People’s Republic of China
Heng Cai: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of China; Liaoning Clinical Medical Research Center in Nervous System Disease, Shenyang 110004, People’s Republic of China; Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang 110004, People’s Republic of China
Di Wang: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of China; Liaoning Clinical Medical Research Center in Nervous System Disease, Shenyang 110004, People’s Republic of China; Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang 110004, People’s Republic of China
Zhen Li: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of China; Liaoning Clinical Medical Research Center in Nervous System Disease, Shenyang 110004, People’s Republic of China; Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang 110004, People’s Republic of China
Lini Zhao: Department of Pharmacology, Shenyang Medical College, Shenyang 110034, People’s Republic of China
Yixue Xue: Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang 110122, People’s Republic of China; Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang 110122, People’s Republic of China; Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang 110122, People’s Republic of China; Corresponding author: Yixue Xue, Department of Neurobiology, School of life Sciences, China Medical University, Shenyang 110122, People’s Republic of China.

Journal volume & issue: Vol. 17
pp. 138 – 152

Abstract

Read online

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.

Published in Molecular Therapy: Oncolytics

ISSN: 2372-7705 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.cell.com/molecular-therapy-family/oncolytics/latest-content

About the journal

Abstract

Keywords