A dual-affinity peptide nucleic acid for targeting miRNA-21 precursor rescues tumor repressor PTEN expression

<h2>Summary</h2> MicroRNAs (miRNAs) are key regulators of gene expression and are related to diseases including cancer. Targeting miRNA precursors (pre-miRs) that contain both double-stranded (ds) and single-stranded (ss) elements remains challenging. We previously developed a dual-affinity peptide nucleic acid (daPNA) platform that combines antisense PNA (asPNA) and dsRNA-binding PNA (dbPNA) to target RNA-junction regions. Here, we apply this platform to target pre-miR-21, a precursor of oncogenic miR-21. The binding data reveal that daPNA-21-10 binds with high specificity and affinity to pre-miR-21, which is not easily targeted by traditional anti-miR, asPNA, or dbPNA. daPNA-21-10 inhibits Dicer processing <i>in vitro</i>. In human cell lines, daPNA-21-10 reduces mature miR-21 level and restores expression of the tumor suppressor PTEN. The daPNA platform is a highly programmable tool for probing and modulating RNA functions, with broad therapeutic potential.

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Publication Details

Journal
Cell Reports Physical Science
Published
2025-11-01
DOI
https://doi.org/10.1016/j.xcrp.2025.102935
Primary Topic
MicroRNA in disease regulation
Type
article
Field-Weighted Citation Impact
0.00
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article

A dual-affinity peptide nucleic acid for targeting miRNA-21 precursor rescues tumor repressor PTEN expression

Jean‐Luc Décout, Clément Dezanet, Albert Ong, Souvik Maiti et al.
Cell Reports Physical Science
MicroRNA in disease regulation
article

A dual-affinity peptide nucleic acid for targeting miRNA-21 precursor rescues tumor repressor PTEN expression

Jean‐Luc Décout, Clément Dezanet, Albert Ong, Souvik Maiti, Rongguang Lu, Desiree‐Faye Kaixin Toh, Tianwei Qian, Kiran M. Patil, Gang Chen, Xuan Zhan, Anni Wang, Xin Ke, Hongwei Wang, Manchugondanahalli S. Krishna, Arpita Ghosh, Yun Lian, Ruiyu Lin
article en

Abstract

<h2>Summary</h2> MicroRNAs (miRNAs) are key regulators of gene expression and are related to diseases including cancer. Targeting miRNA precursors (pre-miRs) that contain both double-stranded (ds) and single-stranded (ss) elements remains challenging. We previously developed a dual-affinity peptide nucleic acid (daPNA) platform that combines antisense PNA (asPNA) and dsRNA-binding PNA (dbPNA) to target RNA-junction regions. Here, we apply this platform to target pre-miR-21, a precursor of oncogenic miR-21. The binding data reveal that daPNA-21-10 binds with high specificity and affinity to pre-miR-21, which is not easily targeted by traditional anti-miR, asPNA, or dbPNA. daPNA-21-10 inhibits Dicer processing <i>in vitro</i>. In human cell lines, daPNA-21-10 reduces mature miR-21 level and restores expression of the tumor suppressor PTEN. The daPNA platform is a highly programmable tool for probing and modulating RNA functions, with broad therapeutic potential.

Cell Reports Physical ScienceVol. 6(11)
Centre National de la Recherche Scientifique (FR), Nanyang Technological University (SG), Institute of Genomics and Integrative Biology (IN), Département de Chimie Moléculaire (FR), Chinese University of Hong Kong, Shenzhen (CN), Université Grenoble Alpes (FR), Tsinghua University (CN), Academy of Scientific and Innovative Research (IN)
Openalex Percentile: Top 57%
MicroRNA in disease regulation
DOIOpen Access PDFOpenAlex
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