Peptide nucleic acids (PNAs) have been demonstrated to be very useful tools for gene regulation at different levels and with different mechanisms of action. In the last few years the use of PNAs for targeting microRNAs (anti-miRNA PNAs) has provided impressive advancements. In particular, targeting of microRNAs involved in the repression of the expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is defective in cystic fibrosis (CF), is a key step in the development of new types of treatment protocols. In addition to the anti-miRNA therapeutic strategy, inhibition of miRNA functions can be reached by masking the miRNA binding sites present within the 3′UTR region of the target mRNAs. The objective of this study was to design a PNA masking the binding site of the microRNA miR-145-5p present within the 3′UTR of the CFTR mRNA and to determine its activity in inhibiting miR-145-5p function, with particular focus on the expression of both CFTR mRNA and CFTR protein in Calu-3 cells. The results obtained support the concept that the PNA masking the miR-145-5p binding site of the CFTR mRNA is able to interfere with miR-145-5p biological functions, leading to both an increase of CFTR mRNA and CFTR protein content.

中文翻译：

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肽核酸 (PNA) 掩盖了囊性纤维化跨膜电导调节因子 (CFTR) mRNA 3'UTR 的 miR-145-5p 结合位点，增强了 Calu-3 细胞中的 CFTR 表达

肽核酸 (PNA) 已被证明是用于不同水平和不同作用机制的基因调控的非常有用的工具。在过去几年中，使用 PNA 靶向 microRNA（抗 miRNA PNA）取得了令人瞩目的进步。特别是，靶向参与抑制囊性纤维化跨膜电导调节剂 (CFTR) 基因表达的 microRNA，在囊性纤维化 (CF) 中存在缺陷，是开发新型治疗方案的关键步骤。除了抗 miRNA 治疗策略外，还可以通过掩盖存在于目标 mRNA 3'UTR 区域内的 miRNA 结合位点来抑制 miRNA 功能。本研究的目的是设计一种 PNA 来掩盖存在于 CFTR mRNA 3'UTR 中的 microRNA miR-145-5p 的结合位点，并确定其抑制 miR-145-5p 功能的活性，特别关注CFTR mRNA和CFTR蛋白在Calu-3细胞中的表达。获得的结果支持这样一个概念，即掩蔽 CFTR mRNA 的 miR-145-5p 结合位点的 PNA 能够干扰 miR-145-5p 的生物学功能，导致 CFTR mRNA 和 CFTR 蛋白含量的增加。