1. Downregulation of miR-218 contributes to epithelial–mesenchymal transition and tumor metastasis in lung cancer by targeting Slug/ZEB2 signaling
- Author
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Xin Ge, Jiang Cf, Stephen C. Peiper, Hongbing Shen, Pan Mh, Zhumei Shi, Bing-Hua Jiang, Ling-Zhi Liu, Jun He, Li Dm, Li W, Y. Shu, Wen Yy, Huiling Sun, and Linjun Wang
- Subjects
0301 basic medicine ,Cancer Research ,Epithelial-Mesenchymal Transition ,Lung Neoplasms ,Slug ,Biology ,Metastasis ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Cell Movement ,microRNA ,Genetics ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Epithelial–mesenchymal transition ,Lung cancer ,Molecular Biology ,Zinc Finger E-box Binding Homeobox 2 ,A549 cell ,Homeodomain Proteins ,Cancer ,Cell migration ,medicine.disease ,biology.organism_classification ,Xenograft Model Antitumor Assays ,3. Good health ,Gene Expression Regulation, Neoplastic ,Repressor Proteins ,MicroRNAs ,030104 developmental biology ,A549 Cells ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Immunology ,embryonic structures ,Cancer research ,Original Article ,Snail Family Transcription Factors ,Cisplatin - Abstract
Epithelial–mesenchymal transition (EMT) has been recognized as a key element of cell migration and invasion in lung cancer; however, the underlying mechanisms are not fully elucidated. Recently, emerging evidence suggest that miRNAs have crucial roles in control of EMT and EMT-associated traits such as migration, invasion and chemoresistance. Here, we found that miR-218 expression levels were significantly downregulated in lung cancer tissues compared with adjacent non-cancerous tissues, and the levels of miR-218 were significantly associated with histological grades and lymph node metastasis. Overexpression of miR-218 inhibited cell migration and invasion as well as the EMT process. Of particular importance, miR-218 was involved in the metastatic process of lung cancer cells in vivo by suppressing local invasion and distant colonization. We identified Slug and ZEB2 as direct functional targets of miR-218. Inverse correlations were observed between miR-218 levels and Slug/ZEB2 levels in cancer tissue samples. In addition, overexpression of miR-218 in H1299 increased chemosensitivity of cells to cisplatin treatment through suppression of Slug and ZEB2. These findings highlight an important role of miR-218 in the regulation of EMT-related traits and metastasis of lung cancer in part by modulation of Slug/ZEB2 signaling, and provide a potential therapeutic strategy by targeting miR-218 in NSCLC.
- Published
- 2017