Conditionally Replicative Adenovirus Controlled by the Stabilization System of AU-Rich Elements Containing mRNA

Autor: Tetsuya Kitamura, Ishraque Ahmed, Elora Hossain, Motoaki Yasuda, Yohei Mikawa, Aya Yanagawa-Matsuda, Umma Habiba, Fumihiro Higashino, Mohammad Towfik Alam, Masanobu Shindoh, Yoshimasa Kitagawa
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cancers
Volume 12
Issue 5
Cancers, Vol 12, Iss 1205, p 1205 (2020)
ISSN: 2072-6694
DOI: 10.3390/cancers12051205
Popis: 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&prime
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.
Databáze: OpenAIRE
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