Mol Cancer:长非编码RNA ZEB1-AS1可表观调控ZEB1和下游分子的表达

2017-09-10 AlexYang MedSci原创

越来越多的研究表明长非编码RNAs(lncRNAs)在肿瘤形成和癌症恶化中起着重要作用。来源于ZEB1启动子区域的lncRNA ZEB1 反义1(ZEB1-AS1)到现在为止,人们对其表达、作用和机制所知甚少。最近,有研究人员利用RACE技术获得了ZEB1-AS1的序列,并利用RNA干扰技术减少ZEB1-AS1的表达,还利用腺病毒表达载体来增加ZEB1-AS1的表达。另外,研究人员利用CHIP和R

越来越多的研究表明长非编码RNAs(lncRNAs)在肿瘤形成和癌症恶化中起着重要作用。来源于ZEB1启动子区域的lncRNA ZEB1 反义1(ZEB1-AS1)到现在为止,人们对其表达、作用和机制所知甚少。最近,有研究人员利用RACE技术获得了ZEB1-AS1的序列,并利用RNA干扰技术减少ZEB1-AS1的表达,还利用腺病毒表达载体来增加ZEB1-AS1的表达。另外,研究人员利用CHIP和RIP技术检测ZEB1-AS1是通过怎样的表观机制来调控ZEB1表达的。CCK8实验、伤口愈合实验和transwell实验用来测量前列腺癌细胞的增殖和迁移。

研究发现,在前列腺癌细胞中,RNAi调控的ZEB1-AS1下调显著抑制了ZEB1,并且人工ZEB1-AS1过表达恢复了ZEB1的表达,这表明ZEB1-AS1可以促进ZEB1的表达。同时,ZEB1-AS1间接的抑制了miR200c表达,却上调了miR200c的靶标BMI1的表达。另外, ZEB1-AS1可结合和招募组蛋白甲基化转移酶MLL1到ZEB1的启动子区域,从而诱导H3K4me3修饰并且激活ZEB1的转录。因此,从生物学上讲,ZEB1-AS1可以促进前列腺癌细胞的增殖和迁移。总之,ZEB1-AS1在前列腺癌中作为一个致瘤基因,并通过表观激活ZEB1和间接调控ZEB1下游分子来起作用。

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    2017-09-12 明天会更好!

    好文章学习了

    0

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