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Hokkaido University Collection of Scholarly and Academic Papers >
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Oncolytic potential of an E4-deficient adenovirus that can recognize the stabilization of AU-rich element containing mRNA in cancer cells
| Title: | Oncolytic potential of an E4-deficient adenovirus that can recognize the stabilization of AU-rich element containing mRNA in cancer cells |
| Authors: | Yanagawa-Matsuda, Aya Browse this author →KAKEN DB | | Mikawa, Yohei Browse this author | | Habiba, Umma Browse this author | | Kitamura, Tetsuya Browse this author →KAKEN DB | | Yasuda, Motoaki Browse this author →KAKEN DB | | Towfik-Alam, Mohammad Browse this author →KAKEN DB | | Kitagawa, Yoshimasa Browse this author →KAKEN DB | | Minowa, Kazuyuki Browse this author →KAKEN DB | | Shindoh, Masanobu Browse this author →KAKEN DB | | Higashino, Fumihiro Browse this author →KAKEN DB |
| Keywords: | adenovirus | | AU-rich element | | ARE-mRNA | | HuR | | E4orf6 |
| Issue Date: | Feb-2019 |
| Publisher: | Spandidos Publications |
| Journal Title: | Oncology reports |
| Volume: | 41 |
| Issue: | 2 |
| Start Page: | 954 |
| End Page: | 960 |
| Publisher DOI: | 10.3892/or.2018.6865 |
| PMID: | 30431137 |
| 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/75080 |
| Appears in Collections: | 歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 東野 史裕
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