microRNA-214 promotes epithelial-mesenchymal transition and metastasis in lung adenocarcinoma by targeting the suppressor-of-fused protein (Sufu)

Abstract

Distant metastasis is the major cause of cancer-related deaths in patients with lung adenocarcinoma (LAD). Emerging evidence reveals that miRNA is critical for tumor metastasis. miR-214 expression has been associated with LAD progression. However, whether and how miR-214 is involved in the development and metastasis of LAD remain unaddressed. Here, we found that the expression of miR-214 was elevated in LAD and correlated positively with LAD metastasis and epithelial-mesenchymal transition (EMT). In addition, we found that miR-214 enhanced the molecular program controlling the EMT of LAD cells and promoted LAD cell metastasis both in vitro and in vivo. This study thus provides the first evidence to show that the miR-214 expression by LAD cells contributes to the EMT and metastasis of LAD. Mechanistically, Sufu was identified as an important miR-214 functional target for the EMT and metastasis of LAD, ectopic expression of Sufu alleviated miR-214 promoted EMT and metastasis. Importantly, the expression of Sufu inversely correlated with the expression of miR-214 and vimentin and positively associated with the expression of E-cadherin in the tumor cells from human LAD patients. Collectively, this study uncovers a previously unappreciated miR-214-Sufu pathway in controlling EMT and metastasis of LAD and suggests that interfering with miR-214 and Sufu could be a viable approach to treat late stage metastatic LAD patients.