Framework Nucleic Acids Enabled Pulmonary Artery Endothelial Cell Growth Inhibition by Targeting microRNA‐152

• Published in: Chembiochem : a European journal of chemical biology 2022-09, Vol.23 (18), p.e202200344-n/a
• Main Authors: You, Zaichun, Huang, Qiuhong, Xu, Lilin, Liu, Xueping, Fu, Juan, Li, Boxuan, Yang, Yi, Li, Shuyi, Qian, Hang, Wang, Guansong
• Format: Article
• Language: English
• Subjects: AKT protein; Apoptosis; Cell Proliferation; Deoxyribonucleic acid; DNA; DNA, Single-Stranded - metabolism; drug delivery; Endothelial cells; Endothelial Cells - metabolism; framework nucleic acids; Humans; Hypoxia; Hypoxia - metabolism; microRNA-152; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Nucleic acids; Nucleic Acids - metabolism; Proto-Oncogene Proteins c-akt - metabolism; pulmonary arterial endothelial cells; Pulmonary arteries; Pulmonary artery; Pulmonary Artery - metabolism; Ribonucleic acid; RNA; Signal transduction; Therapeutic applications; Therapeutic targets; TOR protein; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.202200344

Pulmonary artery vascular endothelial dysfunction plays a pivotal role in the occurrence and progression of pulmonary vascular remodeling (PVR). To address this, aberrantly expressed non‐coding microRNAs (miRNAs) are excellent therapeutic targets in human pulmonary artery endothelial cells (HPAECs). Here, we discovered and validated the overexpression of miRNA‐152 in HPAECs under hypoxia and its role in endothelial cell dysfunction. We constructed a framework nucleic acid nanostructure that harbors six protruding single‐stranded DNA segments that can fully hybridize with miRNA‐152 (DNT‐152). DNT‐152 was efficiently taken up by HPAECs with increasing time and concentration; it markedly induced apoptosis, and inhibited HPAEC growth under hypoxic conditions. Mechanistically, DNT‐152 silenced miRNA‐152 expression and upregulated its target gene Meox2, which subsequently inhibited the AKT/mTOR signaling pathway. These results indicate that miRNA‐152 in HPAECs may be an excellent therapeutic target against PVR, and that framework nucleic acids with carefully designed sequences are promising nanomedicines for noncancerous cells and diseases. One of the images was subsititued during revision. This is the final version of TOC.