Long Non-coding RNAs: Key Regulators of Tumor Epithelial/Mesenchymal Plasticity and Cancer Stemness

Long non-coding RNAs (lncRNAs) are a class of non-coding RNA molecules with transcripts longer than 200bp, which were initially thought to be noise from genomic transcription without biological function. However, since the discovery of H19 in 1980 and Xist in 1990, increasing evidence has shown that lncRNAs regulate gene expression at epigenetic, transcriptional and post-transcriptional levels through specific regulatory actions, and are involved in the development of cancer and other diseases. Despite lower abundance of lncRNAs than that of protein-coding genes with less sequence conservation, lncRNAs have become an intense area of RNA research. They exert diverse biological functions such as inducing chromatin remodeling, recruiting the transcriptional machinery, acting as competitive endogenous RNAs for microRNAs, and modulating protein-protein interactions. Epithelial-mesenchymal transition (EMT) is a developmental process, associated with embryonic development, wound healing, and cancer progression. In the context of oncogenesis, the EMT program is transiently activated and confers migratory/invasive and cancer stem cell (CSC) properties to tumor cells, which are crucial for malignant progression, metastasis, and therapeutic resistance. Accumulating evidence has revealed that lncRNAs play crucial roles in the regulation of tumor epithelial/mesenchymal plasticity (EMP) and cancer stemness. Here, we summarize the emerging roles and molecular mechanisms of lncRNAs in regulating tumor cell EMP and their effects on tumor initiation and progression through regulation of CSCs. We also discuss the potential of lncRNAs as diagnostic and prognostic biomarkers and therapeutic targets.