Research Papers:

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

Haixia Long _, Zhongyu Wang, Junying Chen, Tong Xiang, Qijing Li, Xinwei Diao & Bo Zhu

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Oncotarget. 2015; 6:38705-38718. https://doi.org/10.18632/oncotarget.5478

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Haixia Long1,*, Zhongyu Wang1,*, Junying Chen1, Tong Xiang1, Qijing Li2, Xinwei Diao3, Bo Zhu1,4

1Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China

2Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA

3Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing, China

4Biomedical 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


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.

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