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

// Haixia Long 1, * , Zhongyu Wang 1, * , Junying Chen 1 , Tong Xiang 1 , Qijing Li 2 , Xinwei Diao 3 , Bo Zhu 1, 4 1 Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China 2 Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA 3 Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing, China 4 Biomedical Analysis Center, Third Military Medical University, Chongqing, China * These authors have contributed equally to this work Correspondence to: Xinwei Diao, e-mail: diaoxinwei931@aliyun.com Bo Zhu, e-mail: b.davis.zhu@gmail.com Keywords: miR-214, metastasis, EMT, lung adenocarcinoma, suppressor-of-fused protein Received: May 04, 2015      Accepted: September 28, 2015      Published: October 08, 2015 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.