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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.
FASEB J. 2020 Jul 05 [Online ahead of print]FJ

Abstract

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.

Authors+Show Affiliations

Department of Physiology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, P.R. China.Department of Physiology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, P.R. China.Department of Physiology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, P.R. China.Department of Neurosurgery, General Hospital of Northern Theater Command, Shenyang, P.R. China.Department of Neurobiology, College Basic of Medicine, China Medical University, Shenyang, P.R. China.Graduate School of Jinzhou Medical University, Jinzhou, P.R. China.Department of Physiology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, P.R. China.Department of Physiology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, P.R. China.Department of Physiology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, P.R. China.Department of Physiology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, P.R. China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32623796

Citation

Zhang, Cai, et al. "Lnc00462717 Regulates the Permeability of the Blood-brain Tumor Barrier Through Interaction With PTBP1 to Inhibit the miR-186-5p/Occludin Signaling Pathway." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 2020.
Zhang C, Zhang X, Wang J, et al. Lnc00462717 regulates the permeability of the blood-brain tumor barrier through interaction with PTBP1 to inhibit the miR-186-5p/Occludin signaling pathway. FASEB J. 2020.
Zhang, C., Zhang, X., Wang, J., Di, F., Xue, Y., Lin, X., Zhang, Y., Zhang, H., Zhang, Z., & Gu, Y. (2020). Lnc00462717 regulates the permeability of the blood-brain tumor barrier through interaction with PTBP1 to inhibit the miR-186-5p/Occludin signaling pathway. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology. https://doi.org/10.1096/fj.202000045R
Zhang C, et al. Lnc00462717 Regulates the Permeability of the Blood-brain Tumor Barrier Through Interaction With PTBP1 to Inhibit the miR-186-5p/Occludin Signaling Pathway. FASEB J. 2020 Jul 5; PubMed PMID: 32623796.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lnc00462717 regulates the permeability of the blood-brain tumor barrier through interaction with PTBP1 to inhibit the miR-186-5p/Occludin signaling pathway. AU - Zhang,Cai, AU - Zhang,Xiaoyi, AU - Wang,Jiahong, AU - Di,Fan, AU - Xue,Yixue, AU - Lin,Xiangdan, AU - Zhang,Ying, AU - Zhang,Hong, AU - Zhang,Zhou, AU - Gu,Yanting, Y1 - 2020/07/05/ PY - 2020/01/09/received PY - 2020/04/22/revised PY - 2020/04/30/accepted PY - 2020/7/6/entrez PY - 2020/7/6/pubmed PY - 2020/7/6/medline KW - Lnc00462717 KW - MiR-186-5p KW - Occludin KW - PTBP1 KW - blood-brain tumor barrier (BTB) KW - permeability JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J. N2 - 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. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/32623796/Lnc00462717_regulates_the_permeability_of_the_blood-brain_tumor_barrier_through_interaction_with_PTBP1_to_inhibit_the_miR-186-5p/Occludin_signaling_pathway L2 - https://doi.org/10.1096/fj.202000045R DB - PRIME DP - Unbound Medicine ER -
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