title: Silencing Snail suppresses tumor cell proliferation and invasion by reversing epithelial-to-mesenchymal transition and arresting G2/M phase in non-small cell lung cancer.
abstract: Epithelial-to-mesenchymal transition (EMT) is essential for tumor invasion and metastasis. Snail has been proven to be a key regulator of EMT. Several studies have shown compelling evidence that Snail is also an important regulator of tumor growth and aggression; however, the role of Snail in the cell cycle has not been clarified. We decreased Snail expression by siRNA transfection and lentiviral‑mediated RNAi, to explore the effect of silencing Snail on the tumorigenicity and migration of lung carcinoma (lung cancer) cells. The results showed that silencing Snail conferred significant anti-proliferative activity and inhibited cell migration, tumor growth and metastasis both in vitro and in vivo. To understand the mechanism of these effects, we further investigated correlations among Snail expression, EMT and cell cycle. Significantly, Snail knockdown reversed EMT processes in lung cancer cells. Furthermore, the cyclin-dependent kinase inhibitor P21 was upregulated after silencing Snail. P21 upregulation manifested its tumor suppressor effects and arrested cells in the G2/M phase, not the G1/S phase following Snail depletion in lung cancer cells. These data suggest that silencing Snail decreases the malignant behaviors of lung cancer cells by reversing EMT processes and causing cell cycle defects.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Han
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Han
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Bingjing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
mesh_terms: D000072283:A549 Cells; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002455:Cell Division; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D000071250:Snail Family Transcription Factors / Q000235:genetics*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D034741:RNA, Small Interfering; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors