Growth inhibitory effects of miR-221 and miR-222 in non-small cell lung cancer cells.
Growth inhibitory effects of miR-221 and miR-222 in non-small cell lung cancer cells.
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DOI：
10.1002/cam4.412
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发表时间：
2015-04
期刊：
影响因子：
4
通讯作者：
Hasegawa, Yoshinori
中科院分区：
文献类型：
--
作者：
Yamashita, Ryo;Sato, Mitsuo;Kakumu, Tomohiko;Hase, Tetsunari;Yogo, Naoyuki;Maruyama, Eiichi;Sekido, Yoshitaka;Kondo, Masashi;Hasegawa, Yoshinori
在几种类型的人类癌症中报道了miR-221和miR-222 microRNA的促癌和抗癌作用。先前的研究表明它们在肺癌侵袭性中的致癌作用，尽管只使用了一种细胞系（H460）。为了进一步评估miR-221和miR-222在肺癌中的作用，我们研究了miR-221和miR-222过表达对六种肺癌细胞系（包括H460）以及一种永生化的正常人支气管上皮细胞系HBEC 4的影响。miR-221和miR-222在少数HBEC 4细胞中诱导上皮向间充质转化（EMT）样变化，但出乎意料的是，这两种microRNA都抑制了它们的侵袭性。与之前的报道一致，miR-221和miR-222促进了H460的生长;然而，miR-221抑制了其他四种细胞系的生长，对一种细胞系没有影响，miR-222抑制了三种细胞系的生长，但促进了两种细胞系的生长。这是第一个显示miR-221和miR-222在肺癌细胞中的肿瘤抑制作用的结果，我们专注于阐明其机制。细胞周期和凋亡分析显示，miR-221和miR-222通过S期内阻滞和/或凋亡抑制生长。最后，转染了miR-221或miR-222的肺癌细胞系对S期靶向药物变得更加敏感，这可能是由于S期群体增加。总之，我们的数据是第一个显示miR-221和miR-222对肺癌的肿瘤抑制作用的数据，再次测试了它们作为该疾病治疗剂的潜力。
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.
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影响因子：
6.4
作者：
Elshazley, Momen;Sato, Mitsuo;Hase, Tetsunari;Yamashita, Ryo;Yoshida, Kenya;Toyokuni, Shinya;Ishiguro, Futoshi;Osada, Hirotaka;Sekido, Yoshitaka;Yokoi, Kohei;Usami, Noriyasu;Shames, David S.;Kondo, Masashi;Gazdar, Adi F.;Minna, John D.;Hasegawa, Yoshinori
通讯作者：
Hasegawa, Yoshinori
瞬态但不稳定的Zeb1敲低会大大抑制恶性胸膜间皮瘤细胞的生长。
影响因子：
3.7
作者：
Horio M;Sato M;Takeyama Y;Elshazley M;Yamashita R;Hase T;Yoshida K;Usami N;Yokoi K;Sekido Y;Kondo M;Toyokuni S;Gazdar AF;Minna JD;Hasegawa Y
通讯作者：
Hasegawa Y
影响因子：
2.5
作者：
Howe EN;Cochrane DR;Richer JK
通讯作者：
Richer JK
影响因子：
50.3
作者：
Garofalo M;Di Leva G;Romano G;Nuovo G;Suh SS;Ngankeu A;Taccioli C;Pichiorri F;Alder H;Secchiero P;Gasparini P;Gonelli A;Costinean S;Acunzo M;Condorelli G;Croce CM
通讯作者：
Croce CM
影响因子：
14.9
作者：
Huang, Da Wei;Sherman, Brad T.;Lempicki, Richard A.
通讯作者：
Lempicki, Richard A.