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Conditionally Replicative Adenovirus Controlled by the Stabilization System of AU-Rich Elements Containing mRNA
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| Title: | Conditionally Replicative Adenovirus Controlled by the Stabilization System of AU-Rich Elements Containing mRNA |
| Authors: | Mikawa, Yohei Browse this author | | Alam, Mohammad Towfik Browse this author →KAKEN DB | | Hossain, Elora Browse this author | | Yanagawa-Matsuda, Aya Browse this author →KAKEN DB | | Kitamura, Tetsuya Browse this author →KAKEN DB | | Yasuda, Motoaki Browse this author →KAKEN DB | | Habiba, Umma Browse this author →KAKEN DB | | Ahmed, Ishraque Browse this author | | Kitagawa, Yoshimasa Browse this author →KAKEN DB | | Shindoh, Masanobu Browse this author | | Higashino, Fumihiro Browse this author →KAKEN DB |
| Keywords: | Oncolytic adenovirus | | E1A | | AU-rich element (ARE) | | HuR | | ARE-mRNA | | E1B55k | | Hexon | | TNF-alpha | | c-fos | | LPS |
| Issue Date: | May-2020 |
| Publisher: | MDPI |
| Journal Title: | Cancers |
| Volume: | 12 |
| Issue: | 5 |
| Start Page: | 1205 |
| Publisher DOI: | 10.3390/cancers12051205 |
| Abstract: | AU-rich elements (AREs) are RNA elements that enhance the rapid decay of mRNAs, including those of genes required for cell growth and proliferation. HuR, a member of the embryonic lethal abnormal vision (ELAV) family of RNA-binding proteins, is involved in the stabilization of ARE-mRNA. The level of HuR in the cytoplasm is up-regulated in most cancer cells, resulting in the stabilization of ARE-mRNA. We developed the adenoviruses AdARET and AdAREF, which include the ARE of TNF-alpha and c-fos genes in the 3 ' -untranslated regions of the E1A gene, respectively. The expression of the E1A protein was higher in cancer cells than in normal cells, and virus production and cytolytic activities were also higher in many types of cancer cells. The inhibition of ARE-mRNA stabilization resulted in a reduction in viral replication, demonstrating that the stabilization system was required for production of the virus. The growth of human tumors that formed in nude mice was inhibited by an intratumoral injection of AdARET and AdAREF. These results indicate that these viruses have potential as oncolytic adenoviruses in the vast majority of cancers in which ARE-mRNA is stabilized. |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/78873 |
| 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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