Chengyong Guo, Shuo Liu, Tao Zhang, Jipeng Yang, Zhaohui Liang, Shengkui Lu
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引用次数: 0
Abstract
Pleckstrin homology like domain family A member 2 (PHLDA2) is an imprinted gene expressed in placenta and has been shown to be associated with tumor progression. However, the effect of PHLDA2 on glioma cell growth has not been reported yet. Data based on TCGA database showed that PHLDA2 was up-regulated in glioma tissues. Moreover, PHLDA2 was also elevated in glioma cells. Functional assays showed that siRNA-mediated knockdown of PHLDA2 reduced cell viability of glioma cells and suppressed the cell proliferation. Cell apoptosis of glioma cells was promoted by silencing of PHLDA2 with increased Bax and decreased Bcl-2. Silencing of PHLDA2 reduced protein expression of p62, enhanced LC3 and Beclin1 to promote autophagy. Phosphorylated AKT and mTOR were down-regulated in glioma cells by interference of PHLDA2. In conclusion, downregulation of PHLDA2 inhibited glioma cell proliferation, and promoted cell apoptosis and autophagy through inactivation of AKT/mTOR signaling.
Pleckstrin homology like domain family A member 2 (PHLDA2)是一种在胎盘中表达的印迹基因,已被证明与肿瘤进展有关。然而,PHLDA2对胶质瘤细胞生长的影响尚未见报道。基于TCGA数据库的数据显示,PHLDA2在胶质瘤组织中表达上调。此外,PHLDA2在胶质瘤细胞中也升高。功能分析显示,sirna介导的PHLDA2敲低可降低胶质瘤细胞的活力,抑制细胞增殖。沉默PHLDA2可促进胶质瘤细胞凋亡,Bax升高,Bcl-2降低。PHLDA2的沉默降低了p62蛋白的表达,增强了LC3和Beclin1的表达,促进了自噬。磷酸化AKT和mTOR在胶质瘤细胞中通过PHLDA2的干扰下调。综上所述,下调PHLDA2可抑制胶质瘤细胞增殖,并通过抑制AKT/mTOR信号通路促进细胞凋亡和自噬。
期刊介绍:
The Journal is appropriate for papers on behavioral, biochemical, or cellular aspects of neural function, plasticity, aging or disease. In addition to analyses in the traditional genetic-model organisms, C. elegans, Drosophila, mouse and the zebrafish, the Journal encourages submission of neurogenetic investigations performed in organisms not easily amenable to experimental genetics. Such investigations might, for instance, describe behavioral differences deriving from genetic variation within a species, or report human disease studies that provide exceptional insights into biological mechanisms