一种高效反义riα多聚dnp 21-nt RNA。

Long Shen, Xiaolan Chen, Jui H Wang
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引用次数: 6

摘要

通过体外转录和化学衍生合成了反义抑制剂poly-2'- o -(2,4-二硝基苯基)-5'- ggcugcgugccuccucacugg(反义多dnp RNA-21)。其碱基序列与在MCF-7乳腺癌细胞和A549肺癌细胞中过表达的PKA调控RIalpha亚基(RIalpha/PKA) mRNA中的核苷酸110-130互补。研究发现,具有生物利用性和rnase抗性的反义多聚dnp RNA-21对MCF-7细胞和A549细胞具有50%的抑制浓度(IC50),分别为0.05 nM和4 nM。具有相同多聚dnp寡核苷酸(ODN)平台但碱基序列混乱、义或错配的对照21-nt rna无活性。用反义poly-DNP RNA-21处理MCF-7细胞,既可以消除riα mRNA的稳态浓度,也可以消除riα蛋白的合成。在足够高的浓度下,反义poly-DNP RNA-21通过诱导细胞凋亡的方式选择性杀死靶向癌细胞。反义poly-DNP RNA-21的序列特异性和极低的IC50值表明,它是一种有希望在体内测试的有效抗癌药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A high-efficacy antisense RIalpha poly-DNP 21-nt RNA.

The antisense inhibitor poly-2'-O-(2,4-dinitrophenyl)-5'-GGCUGCGUGCCUCCUCACUGG (antisense poly-DNP RNA-21) has been synthesized by in vitro transcription followed by chemical derivatization. Its base sequence is complementary to that of nucleotides 110-130 in the mRNA of the regulatory RIalpha subunit of PKA (RIalpha/PKA), which is overexpressed in MCF-7 breast cancer cells and A549 lung cancer cells. The bioavailable and RNase-resistant antisense poly-DNP RNA-21 was found to inhibit cell growth with 50% inhibitory concentration (IC50) values of 0.05 nM in MCF-7 cells and 4 nM in A549 cells. The control 21-nt RNAs with the same poly-DNP oligonucleotide (ODN) platform but with scrambled, sense, or mismatched base sequence are inactive. Treatment of MCF-7 cells with antisense poly-DNP RNA-21 abolishes both the steady-state concentration of RIalpha mRNA and the synthesis of RIalpha protein. At sufficiently high concentration, antisense poly-DNP RNA-21 selectively kills the targeted cancer cells by inducing apoptosis. The observed sequence specificity and extremely low IC50 values of antisense poly-DNP RNA-21 suggest that it is a promising candidate for in vivo testing as an effective anticancer agent.

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