RNA Therapeutics Institute
Cancer Biology | Cell Biology | Genetics and Genomics | Molecular Biology | Neoplasms | Therapeutics
MicroRNAs (miRNAs) have increasingly been shown to be involved in human cancer, and interest has grown about the potential use of miRNAs for cancer therapy. miRNA levels are known to be altered in cancer cells, including in non-small cell lung cancer (NSCLC), a subtype of lung cancer that is the most prevalent form of cancer worldwide and that lacks effective therapies. The let-7 miRNA is involved in the regulation of oncogene expression in cells and directly represses cancer growth in the lung. let-7 is therefore a potential molecular target for tumor therapy. However, applications of RNA interference for cancer research have been limited by a lack of simple and efficient methods to deliver oligonucleotides (ONs) to cancer cells. In this study, we have used in vitro and in vivo approaches to show that HCC827 cells internalize hydrophobically modified let-7b miRNAs (hmiRNAs) added directly to the culture medium without the need for lipid formulation. We identified functional let-7b hmiRNAs targeting the HMGA2 mRNA, one of the let-7 target genes upregulated in NSCLC, and show that direct uptake in HCC827 cells induced potent and specific gene silencing in vitro and in vivo. Thus, hmiRNAs constitute a novel class of ONs that enable functional studies of genes involved in cancer biology and are potentially therapeutic molecules.
MicroRNAs, miRNAs, non-small cell lung cancer, RNA interference
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Copyright © 2019 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
Mol Ther Nucleic Acids. 2019 Nov 18;19:267-277. doi: 10.1016/j.omtn.2019.11.008. Link to article on publisher's site
Molecular therapy. Nucleic acids
Segal M, Biscans A, Gilles M, Anastasiadou E, De Luca R, Lim J, Khvorova A, Slack FJ. (2019). Hydrophobically Modified let-7b miRNA Enhances Biodistribution to NSCLC and Downregulates HMGA2 In Vivo. RNA Therapeutics Institute Publications. https://doi.org/10.1016/j.omtn.2019.11.008. Retrieved from https://escholarship.umassmed.edu/rti_pubs/65
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.