Diala, I, Shiohama, Y, Fujita, T, Kotake, Y, Demonacos, C, Krstic-Demonacos, M, Di Leva, G ORCID: https://orcid.org/0000-0001-6759-8682 and Fujii, M (2020) Telomerase inhibition, telomere attrition and proliferation arrest of cancer cells induced by phosphorothioate ASO-NLS conjugates targeting hTERC and siRNAs targeting hTERT. Nucleosides, Nucleotides & Nucleic Acids, 39 (1-3). 407 - 425.

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Abstract

Telomerase activity has been regarded as a critical step in cellular immortalization and carcinogenesis and because of this, regulation of telomerase represents an attractive target for anti-tumor specific therapeutics. Recently, one avenue of cancer research focuses on antisense strategy to target the oncogenes or cancer driver genes, in a sequence specific fashion to down-regulate the expression of the target gene. The protein catalytic subunit, human telomerase reverse transcriptase (hTERT) and the template RNA component (hTERC) are essential for telomerase function, thus theoretically, inhibition of telomerase activity can be achieved by interfering with either the gene expression of hTERT or the hTERC of the telomerase enzymatic complex. The present study showed that phosphorothioate antisense oligonucleotide (sASO)-nuclear localization signal (NLS) peptide conjugates targeting hTERC could inhibit telomerase activity very efficiently at 5 μM concentration but less efficiently at 1 μM concentration. On the other hand, siRNA targeting hTERT mRNA could strongly suppress hTERT expression at 200 nM concentration. It was also revealed that siRNA targeting hTERT could induce telomere attrition and then irreversible arrest of proliferation of cancer cells.

Item Type: Article
Additional Information: The final accepted manuscript and all relevant information can be found at; https://www.tandfonline.com/doi/full/10.1080/15257770.2020.1713357
Uncontrolled Keywords: Cancer cells, telomerase/telomeres, proliferation arrest, hTERT, hTERC, sASO-NLS conjugate, siRNA
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
R Medicine > R Medicine (General)
R Medicine > R Medicine (General) > R735 Medical education. Medical schools. Research
R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering
Depositing User: Symplectic
Date Deposited: 04 May 2020 10:08
Last Modified: 04 May 2020 10:08
URI: https://eprints.keele.ac.uk/id/eprint/7927

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