AUTHOR=Zhou Wei , Liu Libo , Xue Yixue , Zheng Jian , Liu Xiaobai , Ma Jun , Li Zhen , Liu Yunhui TITLE=Combination of Endothelial-Monocyte-Activating Polypeptide-II with Temozolomide Suppress Malignant Biological Behaviors of Human Glioblastoma Stem Cells via miR-590-3p/MACC1 Inhibiting PI3K/AKT/mTOR Signal Pathway JOURNAL=Frontiers in Molecular Neuroscience VOLUME=10 YEAR=2017 URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2017.00068 DOI=10.3389/fnmol.2017.00068 ISSN=1662-5099 ABSTRACT=
This study aims to investigate the effect of Endothelial-Monocyte-Activating Polypeptide-II (EMAP-II) combined with temozolomide (TMZ) upon glioblastoma stem cells (GSCs) and its possible molecular mechanisms. In this study, combination of EMAP-II with TMZ inhibited cell viability, migration and invasion in GSCs, and autophagy inhibitor 3-methyl adenine (3-MA) and chloroquine (CQ) partly reverse the anti-proliferative effect of the combination treatment. Autophagic vacuoles were formed in GSCs after the combination therapy, accompanied with the up-regulation of LC3-II and Beclin-1 as well as the down-regulation of p62/SQSTM1. Further, miR-590-3p was up-regulated and Metastasis-associated in colon cancer 1 (MACC1) was down-regulated by the combination treatment in GSCs; MiR-590-3p overexpression and MACC1 knockdown up-regulated LC3-II and Beclin-1 as well as down-regulated p62/SQSTM1 in GSCs; MACC1 was identified as a direct target of miR-590-3p, mediating the effects of miR-590-3p in the combination treatment. Furthermore, the combination treatment and MACC1 knockdown decreased p-PI3K, p-Akt, p-mTOR, p-S6 and p-4EBP in GSCs; PI3K/Akt agonist insulin-like growth factor-1(IGF-1) partly blocked the effect of the combination treatment. Moreover,