Targeting TdT gene expression in Molt-4 cells by PNA-octaarginine conjugates.

Autor: Montazersaheb S; Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran., Avci ÇB; Faculty of Medicine, Department of Medical Biology, Ege University, Izmir, Turkey., Bagca BG; Faculty of Medicine, Department of Medical Biology, Ege University, Izmir, Turkey., Ay NPO; Faculty of Medicine, Department of Medical Biology, Ege University, Izmir, Turkey., Tarhriz V; Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran., Nielsen PE; Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3, 2200 Copenhagen N, Denmark., Charoudeh HN; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Hejazi MS; Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: msaeidhejazi@yahoo.com.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2020 Dec 01; Vol. 164, pp. 4583-4590. Date of Electronic Publication: 2020 Sep 14.
DOI: 10.1016/j.ijbiomac.2020.09.081
Abstrakt: Peptide nucleic acid (PNA) is an amide based structural nucleic acid mimic with potential applications in gene therapeutic drug discovery. In the present study, we evaluated and compared the effects on gene expression, cell viability and apoptosis of two antisense PNA-d-octaarginine conjugates, targeting sequences at the AUG translation start site or the 5'-UTR of the TdT (terminal deoxynucleotidyl transferase) gene, as well as a sense oligomer corresponding to the 5'-UTR-antisense, in Molt-4 cells. The protein level of TdT was determined by flow cytometry, and qPCR was used for mRNA expression analysis. Mismatch PNAs were used as control to address the sequence/target spcifity of the biological effects. The results showed that treatment with the AUG- and to slightly lesser extent with the 5'-UTR-antisense PNAs reduced the TdT mRNA as wel as the protein level, whereas only very low effect was observed for the 5'-UTR-sense PNA. A parallel effect was observed on reduced cell survival and increased rate of apoptosis. Our findings suggest that antisense PNAs can inhibit expression of the TdT gene and induce apoptosis in Molt-4 cells.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest, financial or otherwise.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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