期刊
NEUROPHARMACOLOGY
卷 110, 期 -, 页码 362-375出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2016.07.038
关键词
Xanthohumol; miR-204-3p; IGFBP2; ERK/c-Fos pathway; Glioblastoma
资金
- Ministry of Science and Technology, Taiwan [MOST103-2320-B-038-038, MOST104-2320-B-038-046, MOST105-2320-B-038-019]
- Shuang Ho Hospital [104TMU-SHH-14]
Xanthohumol (XN), a prenylated chalcone extracted from hop plant Humulus lupulus L. (Cannabaceae), has potential for cancer therapy, including gliomas. Micro (mi)RNAs are small noncoding RNAs that control gene expression. Several miRNAs have been identified to participate in regulating glioma development. However, no studies have demonstrated whether miRNA is involved in XN cytotoxicity resulting in glioma cell death. This study investigated the effects of XN-mediated miRNA expression in activating apoptotic pathways in glioblastoma U87 MG cells. First, we found that XN significantly reduced cell viability and induced apoptosis via pro-caspase-3/8 cleavage and poly(ADP ribose) polymerase (PARP) degradation. We also identified that pro-caspase-9 cleavage, Bcl(2) family expression changes, mitochondrial dysfunction, and intracellular ROS generation also participated in XN-induced glioma cell death. With a microarray analysis, miR-204-3p was identified as the most upregulated miRNA induced by XN cytotoxicity. The extracellular signal-regulated kinase (ERK)/c-Fos pathway was validated to participate in XN-upregulated miR-204-3p expression. With a promoter assay and ChIP analysis, we found that c-Fos dose-dependently bound to the miR-204-3p gene promoter region. Furthermore, miR-204-3p levels decreased in several glioma cell lines compared to astrocytes. Over expression of miR-204-3p enhanced glioma cell apoptosis. IGFBP2, an upregulated regulator of glioma proliferation, was validated by a TCGA analysis as a direct target gene of miR-204-3p. XN's inhibition of the IGFBP2/AKT/Bcl2 pathway via miR-204-3p targeting played a critical role in mediating glioma cell death. These results emphasized that the XN-mediated miR-204-3p network may provide novel therapeutic strategies for future glioblastoma therapy and drug development. (C) 2016 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据