Bone marrow stroma-derived miRNAs as regulators, biomarkers and therapeutic targets of bone metastasis.

Abstract

MicroRNAs (miRNAs) are short, endogenous RNA molecules that have essential roles in regulating gene expression. They control numerous physiological and cellular processes, including normal bone organogenesis and homeostasis, by enhancing or inhibiting bone marrow cell growth, differentiation, functional activity and crosstalk of the multiple cell types within the bone. Hence, elucidating miRNA targets in bone marrow stromal cells has revealed novel regulations during bone development and maintenance. Moreover, recent studies have detailed the capacity for bone stromal miRNAs to influence bone metastasis from a number of primary carcinomas by interfering with bone homeostasis or by directly influencing metastatic tumor cells. Owing to the current lack of good diagnostic biomarkers of bone metastases, such changes in bone stromal miRNA expression in the presence of metastatic lesions may become useful biomarkers, and may even serve as therapeutic targets. In particular, cell-free and exosomal miRNAs shed from bone stromal cells into circulation may be developed into novel biomarkers that can be routinely measured in easily accessible samples. Taken together, these findings reveal the significant role of bone marrow stroma-derived miRNAs in the regulation of bone homeostasis and bone metastasis.