@article{0079dc74110f4a5eb762e7e02e28be61,
title = "A selective Aurora-A 5′-UTR siRNA inhibits tumor growth and metastasis",
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.",
author = "Lai, {Chien Hsien} and Chen, {Ruo Yu} and Hsieh, {Hsing Pang} and Tsai, {Shaw Jenq} and Chang, {Kung Chao} and Yen, {Chia Jui} and Huang, {Yu Chuan} and Liu, {Yao Wen} and Lee, {Jenq Chang} and Lai, {Yi Chien} and Hung, {Liang Yi} and Lin, {Bo Wen}",
note = "Funding Information: The authors thank the Nature Publishing Group language editing service for help with the English editing of this manuscript. RS4; 11 cell line was kindly provided by Dr. Tsai-Yun Chen; A549 and H1299 cell lines were kindly provided by Dr. Jan-Jong Hung; U87-MG and A172 cell lines were kindly provided by Dr. Kwang-Yu Chang; HLF1 cell line was friendly provided by Dr. Ding-Yen Lin. This work was supported by grants (103-2622-B-006-014-CC1, 104-2622-B-006-010-CC1, 105-2622-B-006-004-CC1 and 108-2320-B-006-027) from the Ministry of Science and Technology ( MOST , Taiwan), grant from the Ministry of Health and Welfare ( MOHW , Taiwan; MOHW108-TDU-B-211-124018), and the Center of Applied Nanomedicine, National Cheng Kung University (NCKU, Taiwan) from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education ( MOE , Taiwan). Publisher Copyright: {\textcopyright} 2019 Elsevier B.V.",
year = "2020",
month = mar,
day = "1",
doi = "10.1016/j.canlet.2019.12.031",
language = "English",
volume = "472",
pages = "97--107",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
}