國家衛生研究院 NHRI:Item 3990099045/12370

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Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12370

Title:	A selective Aurora-A 5'-UTR siRNA inhibits tumor growth and metastasis
Authors:	Lai, CH;Chen, RY;Hsieh, HP;Tsai, SJ;Chang, KC;Yen, CJ;Huang, YC;Liu, YW;Lee, JC;Lai, YC;Hung, LY;Lin, BW
Contributors:	Institute of Biotechnology and Pharmaceutical Research
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.
Date:	2020-03-01
Relation:	Cancer Letters. 2020 Mar 1;472:97-107.
Link to:	http://dx.doi.org/10.1016/j.canlet.2019.12.031
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0304-3835&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000509612300010
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85076830039
Appears in Collections:	[Hsing-Pang Hsieh] Periodical Articles

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