Synthetic small inhibiting RNAs:: Efficient tools to inactivate oncogenic mutations and restore p53 pathways
Synthetic small inhibiting RNAs:: Efficient tools to inactivate oncogenic mutations and restore p53 pathways
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DOI：
10.1073/pnas.222406899
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发表时间：
2002-11-12
影响因子：
11.1
通讯作者：
Harel-Bellan, A
中科院分区：
文献类型：
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作者：
Martinez, LA;Naguibneva, I;Harel-Bellan, A
在肿瘤发生过程中，改变抑癌基因和癌基因功能的单碱基对突变频繁发生。在超过50%的人类癌症中，基因组的守护者p53被点突变失活。合成的小抑制RNA(SiRNAs)可以抑制哺乳动物细胞中的基因表达，尽管它们的选择性程度可能会受到扩增机制的影响。在这里，我们证明了在表达这两种形式的细胞中，siRNAs中的单个碱基差异区分了突变型和WTP53，导致WT蛋白功能的恢复。因此，siRNAs可能被用来抑制点突变基因的表达，为选择性、个性化的抗肿瘤治疗提供依据。
Single base pair mutations that alter the function of tumor suppressor genes and oncogenes occur frequently during oncogenesis. The guardian of the genome, p53, is inactivated by point mutation in more than 50% of human cancers. Synthetic small inhibiting RNAs (siRNAs) can suppress gene expression in mammalian cells, although their degree of selectivity might be compromised by an amplification mechanism. Here, we demonstrate that a single base difference in siRNAs discriminates between mutant and WT p53 in cells expressing both forms, resulting in the restoration of WT protein function. Therefore, siRNAs may be used to suppress expression of point-mutated genes and provide the basis for selective and personalized antitumor therapy.