Journal article
Therapeutic potential of chemically modified, synthetic, triplex peptide nucleic acid-based oncomiR inhibitors for cancer therapy
Cancer research (Chicago, Ill.), Vol.81(22), pp.5613-5624
09/21/2021
DOI: 10.1158/0008-5472.CAN-21-0736
PMCID: PMC8595710
PMID: 34548334
Abstract
MicroRNA-155 (miR-155) is overexpressed in various types of lymphomas and leukemias, suggesting that targeting miR-155 could be a potential platform for the development of precision medicine. Here we tested the anti-cancer activity of novel, chemically modified, triplex peptide nucleic acid (PNA)-based antimiRs compared to the current state-of-the-art conventional full length antimiRs. Next-generation modified PNAs that bound miR-155 by Watson-Crick and Hoogsteen domains possessed superior therapeutic efficacy in vivo and ex vivo compared to conventional full-length anti-miR-155. The efficacy of anti-miR-155 targeting in multiple lymphoma cell lines was comprehensively corroborated by gene expression, western blot analysis, and cell viability-based functional studies. Finally, preclinical testing in vivo in xenograft mouse models containing lymphoma cell lines demonstrated that treatment with the miR-155-targeting next generation antimiR resulted in a significant decrease in miR-155 expression followed by reduced tumor growth. These findings support the effective therapeutic application of chemically modified triplex PNAs to target miR-155 to treat lymphoma. Overall, the present proof-of-concept study further implicates the potential for next-generation triplex gamma PNAs to target other miRNAs for treating cancer.
Details
- Title: Subtitle
- Therapeutic potential of chemically modified, synthetic, triplex peptide nucleic acid-based oncomiR inhibitors for cancer therapy
- Creators
- Karishma Dhuri - University of ConnecticutRavinder Reddy Gaddam - University of IowaAjit Vikram - University of IowaFrank J Slack - Harvard Medical SchoolRaman Bahal - University of Connecticut
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.81(22), pp.5613-5624
- DOI
- 10.1158/0008-5472.CAN-21-0736
- PMID
- 34548334
- PMCID
- PMC8595710
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: CA241194
- Language
- English
- Date published
- 09/21/2021
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984359798002771
Metrics
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