Long non-coding RNA regulation of epithelial-mesenchymal transition in cancer metastasis

Abstract

Metastasis is a multistep process starting with the dissemination of tumor cells from a primary site and ending with secondary tumor development in an anatomically distant location. The epithelial-mesenchymal transition (EMT), a process that endows epithelial tumor cells with mesenchymal properties including reduced adhesion and increased motility, is considered a critical step driving the early phase of cancer metastasis. Although significant progress has been made in understanding the molecular characteristics of EMT, the intracellular mechanisms driving transition through the various stages of EMT remain unclear. In recent years, an increasing number of studies have demonstrated the involvement of long non-coding RNAs (lncRNAs) in tumor metastasis through modulating EMT. LncRNAs and their associated signaling networks have now emerged as new players in the induction and regulation of EMT during metastasis. Here we summarize the recent findings and characterizations of several known lncRNAs involved in the regulation of EMT. We will also discuss the potential use of these lncRNAs as diagnostic and prognostic biomarkers as well as therapeutic targets to slow down or prevent metastatic spread of malignant tumors.

Figure 1

Regulatory network in EMT. EMT can be regulated by many signaling pathways, transcription factors, and transcriptional/post-transcriptional regulators.

Figure 2

LncRNAs that are known to regulate EMT processes and their validated targets. A diagram depicts the major signaling pathways through which lncRNAs regulated EMT. Pink oval, names of the signaling pathways; pink square oval, EMT-TFs; blue text, lncRNAs that inhibit EMT; red text, lncRNAs that promote EMT; purple text, miRNAs.