Cancer Medicine | |
Growth inhibitory effects of miR‐221 and miR‐222 in non‐small cell lung cancer cells | |
Ryo Yamashita1  Mitsuo Sato1  Tomohiko Kakumu1  Tetsunari Hase1  Naoyuki Yogo1  Eiichi Maruyama1  Yoshitaka Sekido2  Masashi Kondo1  | |
[1] Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan;Department of Cancer Genetics, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan | |
关键词: Apoptosis; cell cycle; epithelial–mesenchymal transition; lung neoplasms; microRNAs; | |
DOI : 10.1002/cam4.412 | |
来源: Wiley | |
【 摘 要 】
Both pro- and anti-oncogenic roles of miR-221 and miR-222 microRNAs are reported in several types of human cancers. A previous study suggested their oncogenic role in invasiveness in lung cancer, albeit only one cell line (H460) was used. To further evaluate involvement of miR-221 and miR-222 in lung cancer, we investigated the effects of miR-221 and miR-222 overexpression on six lung cancer cell lines, including H460, as well as one immortalized normal human bronchial epithelial cell line, HBEC4. miR-221 and miR-222 induced epithelial-to-mesenchymal transition (EMT)-like changes in a minority of HBEC4 cells but, unexpectedly, both the microRNAs rather suppressed their invasiveness. Consistent with the prior report, miR-221 and miR-222 promoted growth in H460; however, miR-221 suppressed growth in four other cell lines with no effects in one, and miR-222 suppressed growth in three cell lines but promoted growth in two. These are the first results to show tumor-suppressive effects of miR-221 and miR-222 in lung cancer cells, and we focused on clarifying the mechanisms. Cell cycle and apoptosis analyses revealed that growth suppression by miR-221 and miR-222 occurred through intra-S-phase arrest and/or apoptosis. Finally, lung cancer cell lines transfected with miR-221 or miR-222 became more sensitive to the S-phase targeting drugs, possibly due to an increased S-phase population. In conclusion, our data are the first to show tumor-suppressive effects of miR-221 and miR-222 on lung cancer, warranting testing their potential as therapeutics for the disease.Abstract
【 授权许可】
CC BY
© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
【 预 览 】
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