Background: Tumors contain a functional subpopulation of cells that exhibit stem cell properties. These cells, named cancer stem cells (CSCs), play significant roles in the initiation and progression of cancer. Long non-coding RNAs (lncRNAs) can act at the transcriptional, posttranscriptional and translational level. As such, they may be involved in various biological processes such as DNA damage repair, inflammation, metabolism, cell survival, cell signaling, cell growth and differentiation. Accumulating evidence indicates that lncRNAs are key regulators of the CSC subpopulation, thereby contributing to cancer progression. The aim of this review is to overview current knowledge about the functional role and the mechanisms of action of lncRNAs in the initiation, maintenance and regulation of CSCs derived from different neoplasms. These lncRNAs include CTCF7, ROR, DILC, HOTAIR, H19, HOTTIP, ATB, HIF2PUT, SOX2OT, MALAT-1, CUDR, Lnc34a, Linc00617, DYNC2H1-4, PVT1, SOX4 and ARSR Uc.283-plus. Furthermore, we will illustrate how lncRNAs may regulate asymmetric CSC division and contribute to self-renewal, drug resistance and EMT, thus affecting the metastasis and recurrence of different cancers. In addition, we will highlight the implications of targeting lncRNAs to improve the efficacy of conventional drug therapies and to hamper CSC survival and proliferation.
Conclusions: lncRNAs are valuable tools in the search for new targets to selectively eliminate CSCs and improve clinical outcomes. LncRNAs may serve as excellent therapeutic targets because they are stable, easily detectable and expressed in tissue-specific contexts.
Keywords: Cancer stem cells; Differentiation; LncRNAs; Non-coding RNAs; Self-renewal; Stemness.