Journal article
Development of novel antimiRzymes for targeted inhibition of miR-21 expression in solid cancer cells
Molecules, Vol.24(13)
2019
Abstract
MicroRNAs (miRNAs) are short non-coding RNAs that are involved in the regulation of gene expression. Previous reports showed an over-expression of miRNA-21 (miR-21) in various cancer cells, and its up-regulation is closely related to cancer initiation, proliferation and metastasis. In this work, we envisioned the development of novel antimiRzymes (anti-miRNA-DNAzyme) that are capable of selectively targeting and cleaving miR-21 and inhibit its expression in cancer cells using the DNAzyme technique. For this purpose, we have designed different antimiRzyme candidates by systematically targeting different regions of miR-21. Our results demonstrated that RNV541, a potential arm-loop-arm type antimiRzyme, was very efficient (90%) to suppress miR-21 expression in U87MG malignant glioblastoma cell line at 200 nM concentration. In addition, RNV541 also inhibited miR-21 expression (50%) in MDA-MB-231 breast cancer cell line. For targeted delivery, we conjugated RNV541 with a transferrin receptor (TfR) targeting aptamer for TfR-mediated cancer cell delivery. As expected, the developed chimeric structure efficiently delivered the antimiRzyme RNV541 into TfR positive glioblastoma cells. TfR aptamer-RNV541 chimeric construct showed 52% inhibition of miR-21 expression in U87MG glioblastoma cells at 2000 nM concentration, without using any transfection reagents, making it a highly desirable strategy to tackle miR-21 over-expressed malignant cancers. Although these are in vitro based observations, based on our results, we firmly believe that our findings could be beneficial towards the development of targeted cancer therapeutics where conventional therapies face several challenges.
Details
- Title
- Development of novel antimiRzymes for targeted inhibition of miR-21 expression in solid cancer cells
- Authors/Creators
- L.M. Larcher (Author/Creator)T. Wang (Author/Creator)R.N. Veedu (Author/Creator)
- Publication Details
- Molecules, Vol.24(13)
- Publisher
- MDPI
- Identifiers
- 991005543314107891
- Copyright
- © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
- Murdoch Affiliation
- Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.196 Micro & Long Noncoding RNA
- 1.196.68 MicroRNA in Cancer
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Chemistry, Multidisciplinary
- ESI research areas
- Chemistry