"AQP8 promotes glioma proliferation and growth, possibly through the ROS/PTEN/AKT signaling pathway"

作者全名："Zhang, Hao; Sheng, Huajun; Guo, Zhen; Xing, Yu; Liu, Qian; Cai, Ziling; Shen, Zihao; Xia, Qingqian; Zhu, Shujuan"

作者地址："[Zhang, Hao; Sheng, Huajun; Guo, Zhen; Liu, Qian; Cai, Ziling; Shen, Zihao; Xia, Qingqian; Zhu, Shujuan] Chongqing Med Univ, Coll Basic Med, Dept Human Anat, Chongqing 400016, Peoples R China; [Xing, Yu] Chongqing Med Univ, Dept Forens Med, Chongqing 400016, Peoples R China"

通信作者："Zhu, SJ (通讯作者)，Chongqing Med Univ, Coll Basic Med, Dept Human Anat, Chongqing 400016, Peoples R China."

来源：BMC CANCER

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001002675900003

JCR分区：Q2

影响因子：3.4

年份：2023

卷号：23

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Apoptosis; aquaporin-8; Glioma; Proliferation; ROS; PTEN; AKT pathway

摘要："BackgroundThe aquaporin (AQP) family of proteins has been implicated in the proliferation and growth of gliomas. Expression of AQP8 is higher in human glioma tissues than in normal brain tissues and is positively correlated with the pathological grade of glioma, suggesting that this protein is also involved in the proliferation and growth of glioma. However, the mechanism by which AQP8 promotes the proliferation and growth of glioma remains unclear. This study aimed to investigate the mechanism and role of abnormal AQP8 expression in glioma development.MethodsThe dCas9-SAM and CRISPR/Cas9 techniques were used to construct viruses with overexpressed and knocked down AQP8, respectively, and infect A172 and U251 cell lines. The effects of AQP8 on the proliferation and growth of glioma and its mechanism via the intracellular reactive oxygen species (ROS) level were observed using cell clone, transwell, flow cytometry, Hoechst, western blotting, immunofluorescence, and real-time quantitative polymerase chain reaction assays. A nude mouse tumor model was also established.ResultsOverexpression of AQP8 resulted in an increased number of cell clones and cell proliferation, enhanced cell invasion and migration, decreased apoptosis and phosphatase and tensin homolog (PTEN) expression, and increased phosphorylated serine/threonine protein kinase (p-AKT) expression and ROS level, whereas the AQP8 knockdown groups showed opposite results. In the animal experiments, the AQP8 overexpression group had higher tumor volume and weight, whereas the AQP8 knockdown group had lower tumor volume and weight compared with those parameters measured in the control group.ConclusionsOur results preliminary suggest that AQP8 overexpression alters the ROS/PTEN/AKT signaling pathway, promoting the proliferation, migration, and invasion of gliomas. Therefore, AQP8 may be a potential therapeutic target in gliomas."

基金机构：National Natural Science Foundation of China [81502161]; Chongqing Science & Technology Commission [cstc2014jcyjA10028]

基金资助正文：<STRONG> </STRONG>This work was supported by grants from the National Natural Science Foundation of China (grant number 81502161) and the Chongqing Science & Technology Commission (grant number cstc2014jcyjA10028).