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

研究成果: Article

摘要

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.

原文English
頁(從 - 到)97-107
頁數11
期刊Cancer Letters
472
DOIs
出版狀態Published - 2020 三月 1

    指紋

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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