Growth inhibitory effects of miR-221 and miR-222 in non-small cell lung cancer cells

Ryo Yamashita, Mitsuo Sato, Tomohiko Kakumu, Tetsunari Hase, Naoyuki Yogo, Eiichi Maruyama, Yoshitaka Sekido, Masashi Kondo, Yoshinori Hasegawa

研究成果: Article査読

55 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)551-564
ページ数14
ジャーナルCancer Medicine
4
4
DOI
出版ステータスPublished - 01-04-2015
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 放射線学、核医学およびイメージング
  • 癌研究

フィンガープリント

「Growth inhibitory effects of miR-221 and miR-222 in non-small cell lung cancer cells」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル