miR-182 contributes to cell adhesion-mediated drug resistance in multiple myeloma via targeting PDCD4

Abstract

miR-182 is a well-described oncogenic miRNA playing a crucial role in the development of many malignancies. However, the role of miR-182 in multiple myeloma (MM) remains unclear. Here, we demonstrate that adhesion of H929 and MM.1S cells to fibronectin could induce miR-182 expression and decrease PDCD4 expression. Furthermore, miR-182 was found to negatively regulate PDCD4 expression in H929 and MM.1S cells. In addition, PDCD4 down-regulation was required for cell adhesion-mediated drug resistance (CAM-DR). Intriguingly, miR-182 up-regulation could promote CAM-DR in H929 and MM.1S cells. Moreover, miR-182 up-regulation and PDCD4 down-regulation enhanced AKT phosphorylation at Ser473 in both H929 and MM.1S cells. Our data suggest that cell adhesion-mediated miR-182 up-regulation and PDCD4 down-regulation may confer drug resistance via enhancing AKT phosphorylation at Ser473.

Keywords: Cell adhesion-mediated drug resistance; Multiple myeloma; Programmed cell death 4; miR-182.