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

Chien Hsien Lai, Ruo Yu Chen, Hsing Pang Hsieh, Shaw Jenq Tsai, Kung Chao Chang, Chia Jui Yen, Yu Chuan Huang, Yao Wen Liu, Jenq Chang Lee, Yi Chien Lai, Liang Yi Hung, Bo Wen Lin

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)97-107
Number of pages11
JournalCancer Letters
Volume472
DOIs
Publication statusPublished - 2020 Mar 1

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5' Untranslated Regions
Small Interfering RNA
Neoplasm Metastasis
Growth
Neoplasms
Exons
Messenger RNA
Colorectal Neoplasms
RNA Isoforms
Safety
Alternative Splicing
Protein Biosynthesis
Systems Analysis
Heterografts
Protein Isoforms
Animal Models
Cell Line
Lung
locked nucleic acid
Liver

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Lai, Chien Hsien ; Chen, Ruo Yu ; Hsieh, Hsing Pang ; Tsai, Shaw Jenq ; Chang, Kung Chao ; Yen, Chia Jui ; Huang, Yu Chuan ; Liu, Yao Wen ; Lee, Jenq Chang ; Lai, Yi Chien ; Hung, Liang Yi ; Lin, Bo Wen. / A selective Aurora-A 5′-UTR siRNA inhibits tumor growth and metastasis. In: Cancer Letters. 2020 ; Vol. 472. pp. 97-107.
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A selective Aurora-A 5′-UTR siRNA inhibits tumor growth and metastasis. / Lai, Chien Hsien; Chen, Ruo Yu; Hsieh, Hsing Pang; Tsai, Shaw Jenq; Chang, Kung Chao; Yen, Chia Jui; Huang, Yu Chuan; Liu, Yao Wen; Lee, Jenq Chang; Lai, Yi Chien; Hung, Liang Yi; Lin, Bo Wen.

In: Cancer Letters, Vol. 472, 01.03.2020, p. 97-107.

Research output: Contribution to journalArticle

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AU - Lai, Chien Hsien

AU - Chen, Ruo Yu

AU - Hsieh, Hsing Pang

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AU - Chang, Kung Chao

AU - Yen, Chia Jui

AU - Huang, Yu Chuan

AU - Liu, Yao Wen

AU - Lee, Jenq Chang

AU - Lai, Yi Chien

AU - Hung, Liang Yi

AU - Lin, Bo Wen

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