4.5 Article

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

Journal

PATHOLOGY RESEARCH AND PRACTICE
Volume 215, Issue 11, Pages -

Publisher

ELSEVIER GMBH
DOI: 10.1016/j.prp.2019.152603

Keywords

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

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Funding

  1. National Natural Science Foundation of China [81670196]
  2. Six Talent Peaks Project in Jiangsu Province [2015-WSN-097]
  3. Pre-Research Project of Nantong University [17ZY37]

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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.

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