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A selective Aurora-A 5'-UTR siRNA inhibits tumor growth and metastasis.

Authors
  • Lai, Chien-Hsien1
  • Chen, Ruo-Yu1
  • Hsieh, Hsing-Pang2
  • Tsai, Shaw-Jenq3
  • Chang, Kung-Chao4
  • Yen, Chia-Jui5
  • Huang, Yu-Chuan1
  • Liu, Yao-Wen6
  • Lee, Jenq-Chang7
  • Lai, Yi-Chien1
  • Hung, Liang-Yi8
  • Lin, Bo-Wen9
  • 1 Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, 70101, Taiwan. , (Taiwan)
  • 2 Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan, Miaoli County, 35053, Taiwan. , (Taiwan)
  • 3 Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan. , (Taiwan)
  • 4 Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan. , (Taiwan)
  • 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. , (Taiwan)
  • 6 Department of Pathology, Kuo General Hospital, Tainan, 70054, Taiwan. , (Taiwan)
  • 7 Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan. , (Taiwan)
  • 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)
  • 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
Cancer letters
Publication Date
Mar 01, 2020
Volume
472
Pages
97–107
Identifiers
DOI: 10.1016/j.canlet.2019.12.031
PMID: 31875524
Source
Medline
Keywords
Language
English
License
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.

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