MicroRNA-223 delivered by platelet-derived microvesicles promotes lung cancer cell invasion via targeting tumor suppressor EPB41L3

Abstract

Background: Patients with hematogenous metastatic lung cancer displayed significantly increased platelet countand aggregation compared to lung cancer patients without hematogenous metastasis. The mechanism underlyingthe correlation between the lung cancer hematogenous metastasis and platelet activation remains unknown.Results: In the present study, we explored the role of microRNA-223 (miR-223) derived from platelets in modulatinglung cancer cell invasion. Our results demonstrated that platelets from NSCLC patients contain higher level ofmiR-223 than that from healthy subjects. The concentration of miR-223 in the platelet-secreted microvesicles(P-MVs) from NSCLC patients was also increased compared to that from healthy subjects. Incubation of humanlung cancer A549 cells with P-MVs resulted in rapid delivery of miR-223 into A549 cells, in which platelet miR-223targeted EPB41L3 and thus promoted A549 cell invasion. The effect of P-MVs on reducing EPB41L3 in A549 cellsbut promoting tumor cell invasion could be largely abolished by depletion of miR-223 via transfection withmiR-223 antagomir. The role of EPB41L3 in inhibiting A549 cell invasion was further validated by directly downregulatingEPB41L3 via transfecting cells with EPB41L3 siRNA or miR-223 mimic.Conclusions: Our study demonstrates for the first time that platelet-secreted miR-223 via P-MVs can promote lung cancercell invasion via targeting tumor suppressor EPB41L3.