Molecular Regulation of Bone Marrow Metastasis in Prostate and Breast Cancer

Table 2

Role of microRNAs in BM metastasis.

MicroRNAs	Expression	Mechanism of function	Cancer	References
miR-16	Decreased	Inhibits prostate tumor growth through regulation of genes expression such as CDK1 and CDK2	PCa	[61]
miR-141	Increased	Its serum level is increased in patients with bone metastatic PCa and is related to bone metastatic lesion. It has a correlation between ALP levels but not with PSA.	PCa	[62]
miR-143, miR-145	Decreased	Upregulation of them decreases the invasion capacity and EMT. Increased expression inhibits cell viability and colony formation. They suppress tumor sphere formation, expression of CSC markers, and stemness factors such as CD133, CD44, Oct4, C-Myc, and K1f4 in PC-3 cells.; HEF1 gene is a target of miR-145.	PCa	[63–65]
miR-203	Decreased	Its reexpression suppresses metastasis and ectopic expression leads to repression of Runx2 and Smad4 expression.	PCa	[66]
miR-218	Increased	Increases the Wnt activity by downregulating its inhibitors SOST, DKK2, and SFRP2 during osteogenesis, which participate in the homing and growth of metastasized cells to the bone. Also it is stimulated in response to Wnt signaling.	BCa	[67]
miR-224	Increased	Inhibits RKIP gene expression.	BCa	[68]
miR-335	Decreased	SOX4 and TNC are among its target genes. Absence of miR-335 and miR-126 in BCa is associated with poor metastasis free survival.	BCa	[69, 70]
miR-16, miR-378	Increased	Serum levels of sICAM1 and OCL microRNAs-16 and -378 which are increased during OCL differentiation, are associated with bone metastasis.	⋯	[71]

Abbreviations: CDK: cyclin-dependent kinase; PCa: prostate cancer; BCa: breast cancer; ALP: alkaline phosphatase; PSA: prostate-specific antigen; EMT: epithelial-mesenchymal transition; CSC: cancer stem cell; Oct4: octamer-binding transcription factor 4; HEF1: human enhancer of filamentation 1; Runx2: runt-related transcription factor 2; SOST: sclerostin; DKK2: Dickkopf homolog 1; SFRP2: secreted frizzled related-protein 2; RKIP: Raf kinase inhibitor protein; TNC: Tenascin C; sICAM1: soluble intracellular adhesion molecule; OCL: osteoclast.