F1000 Research:研究发现肉瘤中CIP2A表达调控新机制

2014-05-26 紫夕 医学论坛网

澳大利亚和芬兰学者研究发现SP600125(JNK抑制剂)能抑制蛋白磷酸酶2A癌症抑制因子(CIP2A)的蛋白表达,其对表达时间和表达浓度均有限制作用。然而,利用特定小分子干扰RNA(siRNA)消耗c—JUN氨基末端激酶(JNK)1和JNK2激酶都不能降低CIP2A蛋白表达水平,因此需要通过特定方法证实使用激酶小分子抑制剂的治疗结果,例如使用两种不同的靶向特定siRNA。论文2014年8月在线发

澳大利亚和芬兰学者研究发现SP600125(JNK抑制剂)能抑制蛋白磷酸酶2A癌症抑制因子(CIP2A)的蛋白表达,其对表达时间和表达浓度均有限制作用。然而,利用特定小分子干扰RNA(siRNA)消耗c—JUN氨基末端激酶(JNK)1和JNK2激酶都不能降低CIP2A蛋白表达水平,因此需要通过特定方法证实使用激酶小分子抑制剂的治疗结果,例如使用两种不同的靶向特定siRNA。论文2014年8月在线发表于 F1000 Research 。

该研究利用小分子抑制剂对抗p38、MEK和JNK这三大信号通路,明确肉瘤细胞中调控CIP2A表达的通路,从而治疗人纤维肉瘤(HT1080)细胞。之后,利用激酶小分子干扰RNA(siRNA)核实结果。

结果如下:

与之前的观察一致,MEK通路小分子抑制剂(PD98059)降低CIP2A mRNA及蛋白表达。

有趣的是,JNK通路小分子抑制剂SP600125降低CIP2A肿瘤蛋白的mRNA和蛋白水平,而SB203580(p38激酶)抑制剂对HT1080细胞的CIP2A表达作用很小。

但是,JNK1或JNK2激酶所对应的siRNA并没有导致CIP2A表达增加。相反,用作阳性对照的两种不同的CIP2A siRNA则降低了HT1080细胞的JNK2表达。


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    2014-05-28 yangshch
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