microRNA-21 upregulates YAP by inhibiting transcription factor RUNX1 to regulate immunosuppressive ability of myeloid-derived suppressor cells in lung cancer

Background: Lung cancer is one of the most frequently fatal cancers. The microRNA-21 (miR-21) has a known oncogenic function on immune cells in tumors, but its biological role and clinical significance in immunosuppression of lung cancer remains largely enigmatic. Our study aims to explore the role and molecular mechanisms of miR-21 in lung cancer. Methods We observed that miR-21 and YAP were highly expressed, while RUNX1 was poorly expressed in lung cancer tissues and cell lines. The loss- and gain- function approaches were performed to determine the roles of miR-21, RUNX1 or YAP in the immunosuppressive ability of myeloid-derived suppressor cells (MDSCs) in lung cancer. Results MiR-21 inhibition, YAP knockdown or RUNX1 overexpression reduced the proportion of MDSCs in lung cancer tissue and peripheral blood, but increased the proportion of T helper (Th) and CTL. Furthermore, miR-21 inhibition, YAP knockdown or RUNX1 overexpression increased apoptosis of MDSCs, more cells at G0/G1 phase, fewer cells at G2/M phase, but reduced IL-10, TGF-β and GM-CSF levels. The effect of miR-21 and RUNX1 on tumor growth was verified by xenograft tumors in nude mice. Conclusions Taken together, miR-21 upregulates YAP expression by inhibiting RUNX1 and consequently promotes the immunosuppressive ability of MDSCs against lung cancer.