School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 210009 Nanjing, China; Ningxia Key Laboratory of Cerebrocranial Diseases, School of Laboratory Medicine, Ningxia Medical University, Yinchuan 750004, China.
Ningxia Key Laboratory of Cerebrocranial Diseases, School of Laboratory Medicine, Ningxia Medical University, Yinchuan 750004, China.
Eur J Cell Biol. 2015 Jan;94(1):22-31. doi: 10.1016/j.ejcb.2014.10.006. Epub 2014 Nov 6.
Competitive endogenous messenger RNA regulates the transcription of other RNA moleculars through competing for the shared microRNAs. This study was carried out to explore the regulation of AEG-1 messenger RNA as a competitive endogenous RNA in the epithelial-mesenchymal transition and metastasis of lung tumor cells. It is shown that the epithelial-mesenchymal transition was associated with the down-regulation of miR-30a, up-regulation of AEG-1 and mesenchymal markers (Snail and Vimentin); miR-30a inhibited the metastasis of lung tumor A549 cells in vitro, whereas AEG-1 promoted it. These results suggested the potential linkage between miR-30a and genes (AEG-1, Snail and Vimentin) in the epithelial-mesenchymal transition and metastasis of lung tumor cell. It was verified later that the 3'-untranslated regions of AEG-1, Snail and Vimentin bind to miR-30a in A549 cells. Therefore, a competitive endogenous RNAs regulatory network among AEG-1, Snail and Vimentin mediated via competitive binding to miR-30a was proved. That is, the 3'-untranslated region of AEG-1, functioning as the competitive endogenous RNAs, indirectly regulated the expression of Vimentin and Snail in inducing epithelial-mesenchymal transition of human non-small cell lung cancer. In conclusion, our findings demonstrated a competitive endogenous RNAs regulatory network which will help understand the metastasis mechanisms of lung cancer and improve the prevention and treatment of lung cancer.
竞争性内源性信使 RNA 通过与共享 microRNAs 竞争来调节其他 RNA 分子的转录。本研究旨在探讨 AEG-1 信使 RNA 作为竞争性内源性 RNA 在肺肿瘤细胞上皮-间充质转化和转移中的调控作用。研究表明，上皮-间充质转化与 miR-30a 的下调、AEG-1 和间充质标志物（Snail 和 Vimentin）的上调有关；miR-30a 抑制肺肿瘤 A549 细胞的体外转移，而 AEG-1 则促进其转移。这些结果表明 miR-30a 与肺肿瘤细胞上皮-间充质转化和转移相关基因（AEG-1、Snail 和 Vimentin）之间存在潜在联系。后来的验证表明，AEG-1、Snail 和 Vimentin 的 3'-非翻译区在 A549 细胞中与 miR-30a 结合。因此，证明了 AEG-1、Snail 和 Vimentin 通过竞争性结合 miR-30a 介导的竞争性内源性 RNA 调节网络。即 AEG-1 的 3'-非翻译区作为竞争性内源性 RNA，间接调节 Vimentin 和 Snail 的表达，从而诱导人非小细胞肺癌的上皮-间充质转化。总之，我们的研究结果表明了一个竞争性内源性 RNA 调节网络，这将有助于理解肺癌的转移机制，并改善肺癌的预防和治疗。
