Human cancer cells suppress behaviors of endothelial progenitor cells through miR-21 targeting IL6R

Deep vein thrombosis (DVT) is a severe clinical process and has a high rate of fatality. Cancer patients have a high incidence rate of venous thrombosis complication and increase the mortality of cancer patients for 2-8 times. The mechanisms involved in human cancers and venous thrombosis remains unclear. In this study, we determined miR-21 expressed higher in human breast cancer, colon cancer and hepatocellular cancer tissues compared with normal tissues and expressed higher in exosomes of breast cancer and hepatocellular cancer cell lines compared with normal cells. MiR-21 dramatically suppressed proliferation, migration and invasion of endothelial progenitor cells (EPCs), which performed promoting role in thrombus repairment and resolution. High levels of miR-21 in exosomes of human cancers dramatically inhibited behaviors of EPCs, and depletion of miR-21 abrogated the decreased proliferation, migration and invasion of EPCs induced by human cancer cells. Moreover, IL6R (interleukin 6 receptor) was identified to be a direct target of miR-21 and promoted cell proliferation, migration and invasion of EPCs. Therefore, the miR-21-IL6R pathway contributed to behaviors of EPCs and consequently mediated the vein thrombosis in patients with cancer. MiR-21-IL6R pathway based therapeutic methods would be beneficial to decrease the complicated venous thrombosis in cancer patients and promote thrombus resolution.