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

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Abstract

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.

Original languageEnglish
Pages (from-to)551-564
Number of pages14
JournalCancer Medicine
Volume4
Issue number4
DOIs
Publication statusPublished - 01-04-2015

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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    Yamashita, R., Sato, M., Kakumu, T., Hase, T., Yogo, N., Maruyama, E., Sekido, Y., Kondo, M., & Hasegawa, Y. (2015). Growth inhibitory effects of miR-221 and miR-222 in non-small cell lung cancer cells. Cancer Medicine, 4(4), 551-564. https://doi.org/10.1002/cam4.412