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Lnc00462717 regulates the permeability of the blood‐brain tumor barrier through interaction with PTBP1 to inhibit the miR‐186‐5p/Occludin signaling pathway
Author(s) -
Zhang Cai,
Zhang Xiaoyi,
Wang Jiahong,
Di Fan,
Xue Yixue,
Lin Xiangdan,
Zhang Ying,
Zhang Hong,
Zhang Zhou,
Gu Yanting
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202000045r
Subject(s) - occludin , gene knockdown , glioma , downregulation and upregulation , tight junction , polypyrimidine tract binding protein , chemistry , blood–brain barrier , cancer research , microbiology and biotechnology , messenger rna , rna binding protein , biology , biochemistry , gene , endocrinology , central nervous system
Blood‐brain tumor barrier (BTB) severely restricts the efficient delivery of chemotherapeutic drugs into brain tumor tissue, which is a critical obstacle for glioma treatment. Recently, long noncoding RNAs (lncRNAs) have shown as regulation factors of numerous biological processes. In this study, we identified that Lnc00462717 was upregulated in glioma endothelial cells (GECs), and that knockdown of Lnc00462717 significantly increased the BTB permeability. Both bioinformatics and RNA immunoprecipitation (RIP) results revealed that Lnc00462717 interacts with polypyrimidine tract binding protein (PTBP1). Moreover, overexpression of PTBP1 significantly reversed the increase in BTB permeability caused by siLnc00462717. Furthermore, the binding sites between miR‐186 and PTBP1 as well as between miR‐186 and 3'UTR of Occludin mRNA were confirmed by RIP and luciferase assays, respectively. And the interaction of Lnc00462717 and PTBP1 significantly facilitated the binding of PTBP1 to 3'UTR of Occludin mRNA and then blocked the miR‐186‐5p‐induced downregulation of Occludin. In addition, we identified that knockdown of Lnc00462717 or overexpression of miR‐186‐5p increased the accumulation of doxorubicin (Dox) in brain glioma via the ultrafast liquid chromatography‐mass spectrometry system (UFLC–MS/MS system) and decreased the intracranial glioma volume in BALB/c nude mice. Taken together, these results show a novel molecular pathway in BTB that may provide a potential innovative strategy for glioma therapy.