Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, PR China.
Sichuan Clinical Research Center of Neurosurgery, Luzhou, 646000, PR China.
Cell Death Dis. 2022 Jun 2;13(6):516. doi: 10.1038/s41419-021-04481-2.
The current study aimed to investigate the effects associated with SNAI2 on the proliferation of glioma stem cells (GSCs) to elucidate its underlying molecular mechanism in the development of glioma. The expression of Snail family transcriptional repressor 2 (SNAI2) in glioma tissues was initially predicted via bioinformatics analysis and subsequently confirmed by reverse transcription quantitative polymerase chain reaction (RT-qPCR), which revealed that SNAI2 was highly expressed in glioma tissues as well as GSCs, with an inverse correlation with overall glioma patient survival detected. Loss- and gain- of-function assays were performed to determine the roles of SNAI2 and pleckstrin homology domain and leucine rich repeat protein phosphatase 2 (PHLPP2) on GSC viability, proliferation and apoptosis. Data were obtained indicating that SNAI2 promoted the proliferation of GSCs, while overexpressed PHLPP2 brought about a contrasting trend. As detected by chromatin immunoprecipitation, RT-qPCR and agarose gel electrophoresis, SNAI2 bound to the promoter region of PHLPP2 and repressed the transcription of PHLPP2 while SNAI2 was found to inhibit PHLPP2 resulting in activation of the Akt pathway. Finally, the roles of SNAI2 and PHLPP2 were verified in glioma growth in nude mice xenografted with tumor. Taken together, the key findings of the present study suggest that SNAI2 may promote the proliferation of GSCs through activation of the Akt pathway by downregulating PHLPP2.
本研究旨在探讨 SNAI2 对神经胶质瘤干细胞（GSCs）增殖的影响，阐明其在神经胶质瘤发生发展中的潜在分子机制。通过生物信息学分析预测 SNAI2 在神经胶质瘤组织中的表达，随后通过反转录定量聚合酶链反应（RT-qPCR）得到验证，结果表明 SNAI2 在神经胶质瘤组织和 GSCs 中高表达，与总体神经胶质瘤患者的生存呈负相关。通过失活和功能获得实验来确定 SNAI2 和 PH 域和亮氨酸丰富重复蛋白磷酸酶 2（PHLPP2）对 GSC 活力、增殖和凋亡的作用。结果表明 SNAI2 促进 GSCs 的增殖，而过表达的 PHLPP2 则呈现相反的趋势。通过染色质免疫沉淀、RT-qPCR 和琼脂糖凝胶电泳检测到，SNAI2 结合到 PHLPP2 的启动子区域，抑制 PHLPP2 的转录，而 SNAI2 被发现抑制 PHLPP2，从而激活 Akt 通路。最后，在裸鼠移植瘤中验证了 SNAI2 和 PHLPP2 在神经胶质瘤生长中的作用。综上所述，本研究的主要发现表明，SNAI2 可能通过下调 PHLPP2 激活 Akt 通路促进 GSCs 的增殖。
