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Inhibiting mutant KRAS G12D gene expression using novel peptide nucleic acid‑based antisense: A potential new drug candidate for pancreatic cancer

  • Authors:
    • Ayelet Shai
    • Evleen Galouk
    • Reem Miari
    • Hala Tareef
    • Marei Sammar
    • Mouhammad Zeidan
    • Anwar Rayan
    • Mizied Falah
  • View Affiliations / Copyright

    Affiliations: Oncology Department, Galilee Medical Center, Nahariya 2210001, Israel, Ephraim Katzir Department of Biotechnology Engineering, ORT Braude College, Karmiel 2161002, Israel, Molecular Genetics and Virology Laboratory, Al‑Qasemi Center of Research Excellence, Baka El‑Garbiah 30100, Israel, Faculty of Science, Al‑Qasemi Academic College, Baka El‑Garbiah 30100, Israel
    Copyright: © Shai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 130
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    Published online on: February 21, 2022
       https://doi.org/10.3892/ol.2022.13250
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Abstract

KRAS mutations, which are the main cause of the pathogenesis of lethal pancreatic adenocarcinomas, impair the functioning of the GTPase subunit, thus rendering it constitutively active and signaling intracellular pathways that end with cell transformation. In the present study, the AsPC‑1 cell line, which has a G12D‑mutated KRAS gene sequence, was utilized as a cellular model to test peptide nucleic acid‑based antisense technology. The use of peptide nucleic acids (PNAs) that are built to exhibit improved hybridization specificity and have an affinity for complementary RNA and DNA sequences, as well as a simple chemical structure and high biological stability that affords resistance to nucleases and proteases, enabled targeting of the KRAS‑mutated gene to inhibit its expression at the translation level. Because PNA‑based antisense molecules should be capable of binding to KRAS mRNA sequences, PNAs were utilized to target the mRNA of the mutated KRAS gene, a strategy that could lead to the development of a novel drug for pancreatic cancer. Moreover, it was demonstrated that introducing new PNA to cells inhibited the growth of cancer cells and induced apoptotic death and, notably, that it can inhibit G12D‑mutated KRAS gene expression, as demonstrated by RT‑PCR and western blotting. Altogether, these data strongly suggest that the use of PNA‑based antisense agents is an attractive therapeutic approach to treating KRAS‑driven cancers and may lead to the development of novel drugs that target the expression of other mutated genes.
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Copy and paste a formatted citation
Spandidos Publications style
Shai A, Galouk E, Miari R, Tareef H, Sammar M, Zeidan M, Rayan A and Falah M: Inhibiting mutant KRAS G12D gene expression using novel peptide nucleic acid‑based antisense: A potential new drug candidate for pancreatic cancer. Oncol Lett 23: 130, 2022.
APA
Shai, A., Galouk, E., Miari, R., Tareef, H., Sammar, M., Zeidan, M. ... Falah, M. (2022). Inhibiting mutant KRAS G12D gene expression using novel peptide nucleic acid‑based antisense: A potential new drug candidate for pancreatic cancer. Oncology Letters, 23, 130. https://doi.org/10.3892/ol.2022.13250
MLA
Shai, A., Galouk, E., Miari, R., Tareef, H., Sammar, M., Zeidan, M., Rayan, A., Falah, M."Inhibiting mutant KRAS G12D gene expression using novel peptide nucleic acid‑based antisense: A potential new drug candidate for pancreatic cancer". Oncology Letters 23.4 (2022): 130.
Chicago
Shai, A., Galouk, E., Miari, R., Tareef, H., Sammar, M., Zeidan, M., Rayan, A., Falah, M."Inhibiting mutant KRAS G12D gene expression using novel peptide nucleic acid‑based antisense: A potential new drug candidate for pancreatic cancer". Oncology Letters 23, no. 4 (2022): 130. https://doi.org/10.3892/ol.2022.13250
Copy and paste a formatted citation
x
Spandidos Publications style
Shai A, Galouk E, Miari R, Tareef H, Sammar M, Zeidan M, Rayan A and Falah M: Inhibiting mutant KRAS G12D gene expression using novel peptide nucleic acid‑based antisense: A potential new drug candidate for pancreatic cancer. Oncol Lett 23: 130, 2022.
APA
Shai, A., Galouk, E., Miari, R., Tareef, H., Sammar, M., Zeidan, M. ... Falah, M. (2022). Inhibiting mutant KRAS G12D gene expression using novel peptide nucleic acid‑based antisense: A potential new drug candidate for pancreatic cancer. Oncology Letters, 23, 130. https://doi.org/10.3892/ol.2022.13250
MLA
Shai, A., Galouk, E., Miari, R., Tareef, H., Sammar, M., Zeidan, M., Rayan, A., Falah, M."Inhibiting mutant KRAS G12D gene expression using novel peptide nucleic acid‑based antisense: A potential new drug candidate for pancreatic cancer". Oncology Letters 23.4 (2022): 130.
Chicago
Shai, A., Galouk, E., Miari, R., Tareef, H., Sammar, M., Zeidan, M., Rayan, A., Falah, M."Inhibiting mutant KRAS G12D gene expression using novel peptide nucleic acid‑based antisense: A potential new drug candidate for pancreatic cancer". Oncology Letters 23, no. 4 (2022): 130. https://doi.org/10.3892/ol.2022.13250
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