Downregulation of miR-218 contributes to epithelial-mesenchymal transition and tumor metastasis in lung cancer by targeting Slug/ZEB2 signaling.

Authors

• Z-M Shi
• L Wang
• H Shen
• C-F Jiang
• X Ge
• D-M Li
• Y-Y Wen
• H-R Sun
• M-H Pan
• W Li
• Y-Q Shu
• L-Z Liu
• S C Peiper
• J He
• B-H Jiang

Publication/Presentation Date

5-4-2017

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.

Volume

36

Issue

18

First Page

2577

Last Page

2588

ISSN

1476-5594

Published In/Presented At

Shi, Z. M., Wang, L., Shen, H., Jiang, C. F., Ge, X., Li, D. M., Wen, Y. Y., Sun, H. R., Pan, M. H., Li, W., Shu, Y. Q., Liu, L. Z., Peiper, S. C., He, J., & Jiang, B. H. (2017). Downregulation of miR-218 contributes to epithelial-mesenchymal transition and tumor metastasis in lung cancer by targeting Slug/ZEB2 signaling. Oncogene, 36(18), 2577–2588. https://doi.org/10.1038/onc.2016.414

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

28192397

Department(s)

Administration and Leadership

Document Type

Article