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Introduction
The epithelial-mesenchymal transition (EMT), initially recognized as essential during embryonic development, has more recently been implicated in promoting carcinoma invasion and metastasis. The full accomplishment of the EMT process requires a complex genetic program that, together with the loss of the epithelial character, implies the acquisition of mesenchymal and motility properties. EMT can be exploited by normal or tumor epithelial cells to enable them to dissociate from their neighbours and migrate [1]. Several transcription factors have been identified as master regulators of EMT, including Snail, ZEB and Twist families, and their expression is tightly regulated at different steps of transcription, translation and protein stability control by a variety of cell-intrinsic pathways as well as extracellular cues [2]. A full understanding of the gene regulation network during this transition is essential but still far beyond completion.
Long non-coding RNAs (lncRNAs) are a large class of transcripts longer than 200 nucleotides with limited protein coding potential [3]. Presently, only a small number of lncRNAs have been characterized functionally, and most of them are shown to exert their effects by regulating various aspects of gene expression, such as transcription, splicing, translation, protein stability control, etc [4-10] (Fig. 1). Many lncRNAs are shown to regulate important cancer hallmarks, including proliferation [11], senescence [12], apoptosis [13], metablism [14], drug-resistance [15], and metastasis [16, 17]. Metastases are the major cause of death from cancer [18] and probably derived from primary tumor cells that have undergone EMT [19]. Recently, an increasing number of studies report that lncRNAs represent some of the most differentially expressed transcripts between primary and metastatic cancers [20, 21]. Therefore, the crosstalk between lncRNAs and EMT regulators is an important topic in the field of cancer metastasis, and lncRNAs may be the missing links in the well-known EMT networks.
Fig. 1.
[Image omitted. See PDF.]
Models of lncRNA mechanisms of action. (a) lncRNA expression can faithfully reflect the combinatorial actions of transcription factors or signaling pathways to indicate gene regulation in space and time. (b) lncRNAs can act as decoys that titrate away DNA-binding proteins, such as transcription factors. (c) lncRNAs can act as guides to recruit proteins, such as chromatin-modifying enzymes, to target genes. (d) lncRNAs may act as scaffolds to bring two or more...