title: Growth inhibitory effects of miR-221 and miR-222 in non-small cell lung cancer cells.
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.
authors: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors: Ryo
authors: R
authors: Yamashita
authors: Mitsuo
authors: M
authors: Sato
authors: Tomohiko
authors: T
authors: Kakumu
authors: Tetsunari
authors: T
authors: Hase
authors: Naoyuki
authors: N
authors: Yogo
authors: Eiichi
authors: E
authors: Maruyama
authors: Yoshitaka
authors: Y
authors: Sekido
authors: Masashi
authors: M
authors: Kondo
authors: Yoshinori
authors: Y
authors: Hasegawa
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D016196:S Phase / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs; C525709:MIR221, human; C525710:MIR222, human
keywords: Apoptosis; cell cycle; epithelial-mesenchymal transition; lung neoplasms; microRNAs
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