Exosomal microRNA?146a derived from mesenchymal stem cells increases the sensitivity of ovarian cancer cells to docetaxel and taxane via a LAMC2?mediated PI3K/Akt axis

摘要

The carrier role of exosomes from human umbilical cord mesenchymal stem cells (hUCMSCs) containing microRNAs (miRNAs) has been implicated in gene and drug therapy. The aim of the present study was to investigate the role of exosomal microRNA?146a (miR?146a) from hUCMSCs in ovarian cancer (OC). Following the generation of docetaxel (DTX)?resistant SKOV3 cells and taxane?resistant A2780 cells, exosomes were isolated from hUCMSCs and added to the chemoresistant cells. Microarray analysis revealed that miR?146a expression was upregulated in DTX/SKOV3 cells among 15 ectopically expressed miRNAs. Analysis using the StarBase and miRSearch databases demonstrated that miR?146a targeted laminin γ2 (LAMC2), which was further verified using dual?luciferase reporter assays. Subsequently, miR?146a inhibitor or LAMC2 overexpression vectors were transfected into hUCMSCs or OC cells, respectively, and their effects on growth and chemoresistance in OC cells were assessed. The hUCMSC?derived exosomes reduced cell growth and chemoresistance in OC. Furthermore, hUCMSC?derived exosomes with miR?146a expression knocked down increased OC cell growth and chemoresistance, which was mediated by the PI3K/Akt signaling pathway via LAMC2.