“De-coding” Stemness Pathways in Cancer

The discovery of noncoding RNAs (ncRNAs) solved the apparent contradiction between the large extent of the human transcriptome and the relatively small number of protein-coding genes. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) account for the majority of noncoding transcripts with regulatory functions and proved to be important players in cancer onset and progression. Here we highlighted the oncogenic and tumor suppressive roles of ncRNAs, particularly focusing on how they affect cancer stem cells (CSCs)-sustaining signalling pathways. JAK-STAT, TGF-β, WNT and Hedgehog pathways control some major mechanisms fueling the cancer stem cell state, ranging from epithelial-to-mesenchymal transition (EMT) to the crosstalk with the tumor stroma. A further understanding of the mechanisms underlying ncRNAs function in CSCs will lay the foundation for developing therapeutic strategies more effective in selectively targeting the CSC population.