microRNA-214 promotes epithelial-mesenchymal transition and metastasis in lung adenocarcinoma by targeting the suppressor-of-fused protein (Sufu).
microRNA-214 promotes epithelial-mesenchymal transition and metastasis in lung adenocarcinoma by targeting the suppressor-of-fused protein (Sufu).
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microRNA-214通过靶向融合蛋白抑制蛋白（Sufu）促进肺腺癌的上皮-间质转化和转移
DOI：
10.18632/oncotarget.5478
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发表时间：
2015-11-17
期刊：
影响因子：
--
通讯作者：
Zhu B
中科院分区：
文献类型：
--
作者：
Long H;Wang Z;Chen J;Xiang T;Li Q;Diao X;Zhu B
远处转移是肺腺癌(LAD)患者癌症相关死亡的主要原因。越来越多的证据表明，miRNA在肿瘤转移中起着关键作用。MIR-214的表达与LAD的进展有关。然而，miR-214是否以及如何参与LAD的发生和转移仍未阐明。在此，我们发现miR-214在LAD中的表达升高，并且与LAD转移和上皮-间充质转化(EMT)呈正相关。此外，我们还发现miR-214增强了LAD细胞EMT的分子程序，促进了LAD细胞在体内外的转移。本研究首次证实miR-214在LAD细胞中的表达与LAD的EMT和转移有关。从机制上讲，Sufu被认为是LAD EMT和转移的一个重要的miR-214功能靶点，Sufu的异位表达减轻了miR-214促进了LAD的EMT和转移。重要的是，SuFU的表达与MIR-214和Vimentin的表达呈负相关，而与E-钙粘素的表达呈正相关。总之，本研究揭示了一个以前未被认识的miR-214-Sufu通路在控制LAD的EMT和转移中的作用，并提示干扰miR-214和Sufu可能是治疗晚期转移性LAD患者的一种可行的方法。
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.