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Open AccessArticle

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

1
Department of Vascular Biology and Molecular Pathology, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586, Japan
2
Department of Oral Diagnosis and Medicine, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586, Japan
3
Department of Molecular Oncology, Faculty of Dental Medicine and Graduate School of Biomedical Science and Engineering, Hokkaido University, Sapporo 060-8586, Japan
4
Department of Oral Molecular Microbiology, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586, Japan
5
Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo 060-8638, Japan
6
Department of Nutrition, Faculty of Nursing and Nutrition, Tenshi College, Sapporo 065-0013, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to the work.
Cancers 2020, 12(5), 1205; https://doi.org/10.3390/cancers12051205
Received: 31 March 2020 / Revised: 1 May 2020 / Accepted: 6 May 2020 / Published: 11 May 2020
(This article belongs to the Special Issue The Role of Adenovirus in Cancer Therapy)
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-α 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. View Full-Text
Keywords: Oncolytic adenovirus; E1A; AU-rich element (ARE); HuR; ARE-mRNA; E1B55k; Hexon; TNF-α; c-fos; LPS Oncolytic adenovirus; E1A; AU-rich element (ARE); HuR; ARE-mRNA; E1B55k; Hexon; TNF-α; c-fos; LPS
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MDPI and ACS Style

Mikawa, Y.; Towfik Alam, M.; Hossain, E.; Yanagawa-Matsuda, A.; Kitamura, T.; Yasuda, M.; Habiba, U.; Ahmed, I.; Kitagawa, Y.; Shindoh, M.; Higashino, F. Conditionally Replicative Adenovirus Controlled by the Stabilization System of AU-Rich Elements Containing mRNA. Cancers 2020, 12, 1205. https://doi.org/10.3390/cancers12051205

AMA Style

Mikawa Y, Towfik Alam M, Hossain E, Yanagawa-Matsuda A, Kitamura T, Yasuda M, Habiba U, Ahmed I, Kitagawa Y, Shindoh M, Higashino F. Conditionally Replicative Adenovirus Controlled by the Stabilization System of AU-Rich Elements Containing mRNA. Cancers. 2020; 12(5):1205. https://doi.org/10.3390/cancers12051205

Chicago/Turabian Style

Mikawa, Yohei; Towfik Alam, Mohammad; Hossain, Elora; Yanagawa-Matsuda, Aya; Kitamura, Tetsuya; Yasuda, Motoaki; Habiba, Umma; Ahmed, Ishraque; Kitagawa, Yoshimasa; Shindoh, Masanobu; Higashino, Fumihiro. 2020. "Conditionally Replicative Adenovirus Controlled by the Stabilization System of AU-Rich Elements Containing mRNA" Cancers 12, no. 5: 1205. https://doi.org/10.3390/cancers12051205

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