miR-218 in breast cancer: friend or foe?

Abstract

miRNAs are small molecules which influence cellular function by regulating the expression of mRNA. They control various stages of the cell’s existence, including differentiation, proliferation and finally death. In cancer cells, miRNAs can become dysregulated, enabling the cell to escape growth suppression and resist apoptosis, as well as adapt to new niches for metastasis. In breast cancer, miR-218 has been shown to play an important role, however, data is conflicting as to its oncogenic or tumour-suppressive impact. Our review aims to assess these differences and identify their potential causes. On one hand, research shows that miR-218 allows breast cancer cells to proliferate and migrate through activation of the EGFR/ErbB2 signalling pathway, as well as metastasize especially to bone tissue, by disrupting the osteogenesis-osteolysis equilibrium. However, data suggesting a tumour-suppressive function point to the role of miR-218 as an enhancer of chemo- and radiosensitivity, as well as an inhibitor of cell proliferation by acting on mTOR. Several studies correlate higher miR-218 expression with better outcomes in patients. It is also part of a subtle network of RNA regulator systems through its interplay with long-noncoding RNA. We hypothesize that these differences in the directionality of miR-218 stem mainly from the cell’s internal state, as well as interactions with its environment. Factors affecting different miRNA expression may include nutrient availability and phenotypic characteristics of the cancer. Therefore, to increase the viability of miR-218 as a therapeutic target, its exact role and context-dependence must be determined.