microRNAs in cancer stem cells: Biology, pathways, and therapeutic opportunities

Cancer stem cells (CSCs) are a small subpopulation of tumor cells that have been identified in most types of cancer. Features that distinguish them from the bulk of tumor cells include their pluripotency, self-renewal capacity, low proliferation rate, and tumor-initiating ability. CSCs are highly malignant, as they confer drug resistance and facilitate tumor progression, relapse, and metastasis. The molecular mechanisms underlying CSC biology are now beginning to be understood. In this context, microRNAs (miRNAs) occupy a prominent place. These endogenous, small noncoding RNA molecules control gene expression at the posttranscriptional level. This study reviews our current understanding of how the misexpression of tumor suppressor and oncogenic miRNAs in CSCs sustain their abundance and malignant properties. We discuss how they partly do so by acting on major CSC signaling pathways, including the Wnt, Notch, Hedgehog, and BMI-1 pathways. Our current knowledge of miRNA functions in CSCs may now be used for cancer diagnostic and prognostic purposes. In addition, when combined with recent technical advances in the in vivo delivery of miRNAs, we are now in an excellent position to develop strategies that harness miRNA interference and replacement technologies for the therapeutic targeting of CSCs.