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Front Mol Neurosci：HOTAIR或为胶质瘤的治疗提供新的靶标

2017-10-02 MedSci MedSci原创

胶质瘤HOTAIR
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研究已证实长链非编码RNA（lncRNA）的Homeobox转录反义中间体RNA（HOTAIR）在各种肿瘤的生物学特性中发挥着关键的作用。本研究旨在探究HOTAIR在体外调节血液肿瘤屏障（BTB）渗透性的作用和可能的分子机制。本课题组既往研究发现神经胶质瘤微血管内皮细胞（GECs）中HOTAIR和上游刺激因子1（USF1）的表达上调，而miR-148b-3p的表达下调。敲除HOTAIR可增加BTB

研究已证实长链非编码RNA（lncRNA）的Homeobox转录反义中间体RNA（HOTAIR）在各种肿瘤的生物学特性中发挥着关键的作用。本研究旨在探究HOTAIR在体外调节血液肿瘤屏障（BTB）渗透性的作用和可能的分子机制。

本课题组既往研究发现神经胶质瘤微血管内皮细胞（GECs）中HOTAIR和上游刺激因子1（USF1）的表达上调，而miR-148b-3p的表达下调。敲除HOTAIR可增加BTB的渗透性，并且下调GEC中紧密连接相关蛋白ZO-1、闭合蛋白及紧密连接蛋白-5的水平，但可上调miR-148b-3p的表达水平。同时，双荧光素酶报告基因分析表明，HOTAIR是miR-148b-3p的靶RNA。此外，miR-148b-3p的过表达通过下调GEC中紧密连接相关蛋白和USF1的表达来增加BTB的通透性，反之亦然。进一步研究结果显示USF1是miR-148b-3p的靶标。沉默USF1提高BTB的渗透性，其原因是与GECs中ZO-1启动子、闭合蛋白和claudin-5相互作用所致。

总之，本研究结果表明，敲低HOTAIR可通过结合miR-148b-3p增加了BTB的通透性，通过靶向USF1进一步减少GEC中的紧密连接相关蛋白的水平。因此，HOTAIR或可作为BTB药物递送的潜在目标，并可能为胶质瘤的治疗提供新的策略。

原始出处：

Libo Sa, Yan Li, Lini Zhao, et al., The Role of HOTAIR/miR-148b-3p/USF1 on Regulating the Permeability of BTB. Front Mol Neurosci. 2017; 10: 194. Published online 2017 Jun 28. doi: 10.3389/fnmol.2017.00194.

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    2018-05-31 weihongyv

    #HOTAIR#

    0

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    2017-10-04 zhaojie88

    #靶标#

    0

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    2017-10-04 lsndxfj

    #ROS#

    0

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    2017-10-02 hhh678

    henhao

    0

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    2017-10-02 131****1460

    学习了受益匪浅

    0

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