Periphery immunocytes may secrete tumor-suppressive 4SC-202 datasheet miRNAs to block tumor growth and propagation. MiRNAs are important modulators of tumor-associated angiogenesis. The miR-17-92 cluster, which includes miR-17, miR-18a, miR-19a/b, miR-20a, and miR-92a, has been linked to tumor angiogenesis. Overexpression of the entire miR-17-92 cluster in myc-induced tumors has been found to increase angiogenesis by paracrine signaling [66]. However, overexpression of the individual members of the miR-17-92 cluster reduced endothelial cell sprouting,

while inhibitors of these miRNAs augmented angiogenesis in vitro, APR-246 chemical structure indicating that the miR-17-92 cluster provides a cell-intrinsic antiangiogenic activity in endothelial cells [67]. Another study by Grange et al. [68] found that microvesicles released from CD105+ renal cancer stem cells, in which 57 miRNAs were differentially

expressed, contributed to triggering the angiogenic switch and coordinating metastatic diffusion during tumor progression. While miR-27b and let-7f were described as proangiogenic miRNAs, miR-221 and miR-222 were identified as antiangiogenic miRNAs in endothelial cells [69–71]. MiRNAs may also influence angiogenesis by acting on endothelial progenitor cells (EPCs) since EPCs play an important role in neovascularization. miR-34a was reported as a tumor suppressor and regulates cell cycle, senescence, apoptosis, and metabolism [72, 73]. A recent study found that overexpression of miR-34a in EPCs impaired EPC-mediated CP673451 angiogenesis by inducing senescence via the inhibition of silent information regulator 1 (SIRT 1). This study provided a mechanistic insight on miRNA-mediated regulation of EPC function [74]. The question of whether in the course of EPC homing to tumor cells, Parvulin circulating miRNAs have some specific function remains unanswered. They could

conceivably act as chemokines, which direct EPCs to tumor neovessels and promote vessel growth [75]. This topic certainly warrants further investigation. Application of circulating miRNAs Their stability and predictive property make miRNAs ideal serum and plasma biomarkers in cancer patients. A variety of independent studies have successfully proved the importance of miRNAs as a tool of cancer diagnosis. Wu and colleagues found that miR-21and miR-29 were significantly upregulated in the serum of breast cancer patients and may be useful biomarkers for breast cancer detection [76, 77]. In non-small cell lung cancer (NSCLC), the expressions of miR-1254 and miR-574-5p were significantly increased with respect to controls. They were able to discriminate tumor samples from controls with 82% and 77% sensitivity and specificity, respectively, as judged by the use of a receiver operating characteristic (ROC) curve [78]. Wei et al.