Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang City, China.
J Neurogenet. 2022 Mar-Jun;36(2-3):74-80. doi: 10.1080/01677063.2022.2096023. Epub 2022 Jul 27.
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.
PHLDA2 基因是一种印迹基因，在胎盘组织中表达，已有研究表明其与肿瘤的发生发展相关。然而，PHLDA2 对神经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 在神经胶质瘤组织中呈上调表达。此外，在神经胶质瘤细胞中 PHLDA2 的表达水平也升高。功能实验表明，通过 siRNA 介导的 PHLDA2 敲低可降低神经胶质瘤细胞的活力，抑制细胞增殖。通过沉默 PHLDA2，促进 Bax 增加和 Bcl-2 减少，促进神经胶质瘤细胞的细胞凋亡。沉默 PHLDA2 可降低 p62 的蛋白表达，增强 LC3 和 Beclin1 促进自噬。干扰 PHLDA2 可下调神经胶质瘤细胞中磷酸化 AKT 和 mTOR 的表达。综上所述，下调 PHLDA2 通过抑制 AKT/mTOR 信号通路，抑制神经胶质瘤细胞的增殖，并促进细胞凋亡和自噬。
