MicroRNA-mediated regulation of bone metastasis formation: from primary tumors to skeleton

MicroRNAs (miRNAs) are highly conserved, small RNAs molecules that regulate gene expression. The functional consequence of miRNA deregulation in cancer and metastasis lies in the mRNA targets whose expression is altered. MiRNA networks acting as upstream regulators of these mRNAs interfere with the initial steps of tumor cell invasion and intravasation, mainly by regulating the epithelial-mesenchymal transition, the motility, invasiveness and survival abilities of cancer cells. The miRNA-mediated regulation of the steps associated with tumor cell tropism, anchorage, homing and colonization of the bone marrow is tissue-specific, being dependent on the regulation by miRNAs of a series of targeted mRNAs in bone marrow sinusoids, bone cells and the bone marrow microenvironment. In this respect, miRNA specific expression signatures that can distinguish between primary tumors and bone metastases might be clinically useful. The identification of metastatic bone-associated changes in miRNA expression suggests that miRNAs may be used as prognostic factors of bone relapse and that the manipulation of miRNA levels may represent a new therapeutic strategy to interfere with bone metastasis.