Micro RNA Regulation of Cancer Stem Cell Phenotypes

Abstract

A small subpopulation of cancer cells, termed Cancer Stem Cells (CSCs), are primarily responsible for initiating metastasis, resistance to therapy and ultimately patient relapse. If any improvements in long- term patient survival are to be achieved, it is vital to target this highly tumorigenic population of cells. The cancer stem-like phenotype is defined by the capability to self-renew, differentiate and proliferate. A number of signaling pathways and stem cell markers have been demonstrated to regulate these vital activities, including Wnt/β- catenin, Hedgehog, Notch, BMI-1 and HMGA2. Intense interest is now focused on developing strategies to eliminate the CSC population. In this regard, several microRNAs (miRNAs), including miR-451, miR- 34a, miR-17-92 and miR-200, have been demonstrated to regulate these fundamental CSC signaling pathways and consequently modulate the CSC phenotype. Thus, modulation of CSC-related miRNAs may represent a plausible mechanism for targeting the CSC population. The pleiotropic nature of miRNA activity can be exploited in a therapeutic manner to simultaneously inhibit multiple key regulators of the CSC phenotype and potentially achieve more efficacious targeting. This article will review our current understanding of the role of miRNAs in regulating CSC signaling pathways. In particular, this review will provide a better understanding of the role of specific miRNAs in regulating the key CSC signaling pathways and highlight several miRNAs that could be therapeutically applicable to eliminate the CSC population.