A selective Aurora-A 5'-UTR siRNA inhibits tumor growth and metastasis.
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Authors
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Lai, Chien-Hsien1
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Chen, Ruo-Yu1
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Hsieh, Hsing-Pang2
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Tsai, Shaw-Jenq3
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Chang, Kung-Chao4
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Yen, Chia-Jui5
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Huang, Yu-Chuan1
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Liu, Yao-Wen6
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Lee, Jenq-Chang7
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Lai, Yi-Chien1
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Hung, Liang-Yi8
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Lin, Bo-Wen9
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1
Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, 70101, Taiwan.
,
(Taiwan)
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2
Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan, Miaoli County, 35053, Taiwan.
,
(Taiwan)
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3
Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan.
,
(Taiwan)
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4
Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan.
,
(Taiwan)
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5
Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan.
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(Taiwan)
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6
Department of Pathology, Kuo General Hospital, Tainan, 70054, Taiwan.
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(Taiwan)
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7
Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan.
,
(Taiwan)
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8
Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, 70101, Taiwan; Ph.D. Program for Cancer Molecular Biology and drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. Electronic address: [email protected]
,
(Taiwan)
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9
Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan. Electronic address: [email protected]
,
(Taiwan)
- Type
- Published Article
- Journal
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Cancer letters
- Publication Date
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Mar 01, 2020
- Volume
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472
- Pages
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97–107
- Identifiers
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DOI: 10.1016/j.canlet.2019.12.031
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PMID: 31875524
- Source
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Medline
- Keywords
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- Language
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English
- License
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Unknown
Abstract
Many Aurora-A inhibitors have been developed for cancer therapy; however, the specificity and safety of Aurora-A inhibitors remain uncertain. The Aurora-A mRNA yields nine different 5'-UTR isoforms, which result from mRNA alternative splicing. Interestingly, we found that the exon 2-containing Aurora-A mRNA isoforms are predominantly expressed in cancer cell lines as well as human colorectal cancer tissues, making the Aurora-A mRNA exon 2 a promising treatment target in Aurora-A-overexpressing cancers. In this study, a selective siRNA, siRNA-2, which targets Aurora-A mRNA exon 2, was designed to translationally inhibit the expression of Aurora-A in cancer cells but not normal cells; locked nucleic acid (LNA)-modified siRNA-2 showed improved efficacy in inhibiting Aurora-A mRNA translation and tumor growth. Xenograft animal models combined with noninvasion in vivo imaging system (IVIS) analysis further confirmed the anticancer effect of LNA-siRNA-2 with improved efficiency and safety and reduced side effects. Mice orthotopically injected with colorectal cancer cells, LNA-siRNA-2 treatment not only inhibited the tumor growth but also blocked liver and lung metastasis. The results of our study suggest that LNA-siRNA-2 has the potential to be a novel therapeutic agent for cancer treatment. Copyright © 2019 Elsevier B.V. All rights reserved.
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
This record was last updated on 08/13/2020 and may not reflect the most current and accurate biomedical/scientific data available from NLM.
The corresponding record at NLM can be accessed at
https://www.ncbi.nlm.nih.gov/pubmed/31875524
