Therapeutic potential of chemically modified, synthetic, triplex peptide nucleic acid-based oncomiR inhibitors for cancer therapy

Cancer Res. 2021 Sep 21:canres.0736.2021. doi: 10.1158/0008-5472.CAN-21-0736. Online ahead of print.ABSTRACTMicroRNA-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.PMID:34548334 | DOI:10.1158/0008-5472.CAN-21-0736
Source: Cell Research - Category: Cytology Authors: Source Type: research