Exploitation of a Very Small Peptide Nucleic Acid as a New Inhibitor of miR-509-3p Involved in the Regulation of Cystic Fibrosis Disease-Gene Expression
Exploitation of a Very Small Peptide Nucleic Acid as a New Inhibitor of miR-509-3p Involved in the Regulation of Cystic Fibrosis Disease-Gene Expression
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DOI：
10.1155/2014/610718
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发表时间：
2014-01-01
影响因子：
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通讯作者：
Castaldo, Giuseppe
中科院分区：
文献类型：
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作者：
Amato, Felice;Tomaiuolo, Rossella;Castaldo, Giuseppe
计算技术，特别是分子动力学(MD)模拟已成功地作为一种补充技术用于预测和分析核酸的结构行为，包括肽核酸-(PNA-)RNA杂交物。本研究表明，与参与CFTR病-囊性纤维化基因转录后调控的miR-509-3P种子区互补的7碱基长的PNA，其N端和C端具有适当的功能，旨在提高其对核酸酶的抗性和细胞摄取，能够逆转含有该基因3‘UTR区的荧光素酶基因在A549人肺癌细胞中的表达，这与MD结果一致，表明尽管后者序列较短，但仍形成了稳定的RNA/PNA异源双链。本文报道的结果扩大了人们对使用小分子PNA作为有效的抗miRNA试剂的兴趣。
Computational techniques, and in particular molecular dynamics (MD) simulations, have been successfully used as a complementary technique to predict and analyse the structural behaviour of nucleic acids, including peptide nucleic acid-(PNA-) RNA hybrids. This study shows that a 7-base long PNA complementary to the seed region of miR-509-3p, one of the miRNAs involved in the posttranscriptional regulation of the CFTR disease-gene of Cystic Fibrosis, and bearing suitable functionalization at its Nand C-ends aimed at improving its resistance to nucleases and cellular uptake, is able to revert the expression of the luciferase gene containing the 3 ' UTR of the gene in A549 human lung cancer cells, in agreement with the MD results that pointed at the formation of a stable RNA/PNA heteroduplex notwithstanding the short sequence of the latter. The here reported results widen the interest towards the use of small PNAs as effective anti-miRNA agents.