Open AccessGrowth inhibitory effects of miR‐221 and miR‐222 in non‐small cell lung cancer cells
Author(s) -
Yamashita Ryo,
Sato Mitsuo,
Kakumu Tomohiko,
Hase Tetsunari,
Yogo Naoyuki,
Maruyama Eiichi,
Sekido Yoshitaka,
Kondo Masashi,
Hasegawa Yoshinori
Publication year - 2015
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.412
Subject(s) - microrna , lung cancer , cancer research , apoptosis , cell growth , cell culture , cell cycle , transfection , biology , growth inhibition , cell , population , cancer , medicine , genetics , gene , environmental health
Both pro‐ and anti‐oncogenic roles of miR‐221 and miR‐222 micro RNA s 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, HBEC 4. miR‐221 and miR‐222 induced epithelial‐to‐mesenchymal transition ( EMT )‐like changes in a minority of HBEC 4 cells but, unexpectedly, both the micro RNA s 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.