Oncolytic potential of an E4-deficient adenovirus that can recognize the stabilization of AU-rich element containing mRNA in cancer cells

  • Authors:
    • Aya Yanagawa-Matsuda
    • Yohei Mikawa
    • Umma Habiba
    • Tetsuya Kitamura
    • Motoaki Yasuda
    • Mohammad Towfik-Alam
    • Yoshimasa Kitagawa
    • Kazuyuki Minowa
    • Masanobu Shindoh
    • Fumihiro Higashino
  • View Affiliations

  • Published online on: November 12, 2018     https://doi.org/10.3892/or.2018.6865
  • Pages: 954-960
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Abstract

AU-rich elements (AREs) are RNA elements that enhance the rapid decay of mRNA. The fate of ARE-mRNA is controlled by ARE-binding proteins. HuR, a member of the embryonic lethal abnormal vision (ELAV) family of RNA-binding proteins, is involved in the export and stabilization of ARE-mRNA. In the vast majority of cancer cells, HuR constitutively relocates to the cytoplasm, resulting in the stabilization of ARE-mRNA. Previously, we described that the adenovirus gene product, E4orf6, which is necessary for virus replication, participates in ARE-mRNA export and stabilization. In the present study, we showed the oncolytic potential of E4orf6-deleted adenovirus dl355, which is expected to be replicated selectively in cancer cells. Virus production and cytolytic activity of dl355 were higher in cancer cells than in normal cells. HuR-depletion downregulated dl355 replication, demonstrating that ARE-mRNA stabilization is required for the production of this virus. Tumor growth was inhibited in nude mice by an intratumoral injection of dl355. Furthermore, dl355 had a stronger oncolytic effect than E1B55k-deleted adenovirus. These results indicate that dl355 has potential as an oncolytic adenovirus for a large number of cancers where ARE-mRNA is stabilized.

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Copy and paste a formatted citation
APA
Yanagawa-Matsuda, A., Mikawa, Y., Habiba, U., Kitamura, T., Yasuda, M., Towfik-Alam, M. ... Higashino, F. (2019). Oncolytic potential of an E4-deficient adenovirus that can recognize the stabilization of AU-rich element containing mRNA in cancer cells. Oncology Reports, 41, 954-960. https://doi.org/10.3892/or.2018.6865
MLA
Yanagawa-Matsuda, A., Mikawa, Y., Habiba, U., Kitamura, T., Yasuda, M., Towfik-Alam, M., Kitagawa, Y., Minowa, K., Shindoh, M., Higashino, F."Oncolytic potential of an E4-deficient adenovirus that can recognize the stabilization of AU-rich element containing mRNA in cancer cells". Oncology Reports 41.2 (2019): 954-960.
Chicago
Yanagawa-Matsuda, A., Mikawa, Y., Habiba, U., Kitamura, T., Yasuda, M., Towfik-Alam, M., Kitagawa, Y., Minowa, K., Shindoh, M., Higashino, F."Oncolytic potential of an E4-deficient adenovirus that can recognize the stabilization of AU-rich element containing mRNA in cancer cells". Oncology Reports 41, no. 2 (2019): 954-960. https://doi.org/10.3892/or.2018.6865