Lu Yongzhi, Sun Wei, Zhang Liang, Li Junyao
Department of Oncology, Qingdao Municipal Hospital, Qingdao, Shandong Province 266000, People's Republic of China.
Department of Neurology, Qingdao Third People's Hospital, Qingdao, Shandong Province 266000, People's Republic of China.
Onco Targets Ther. 2019 Nov 13;12:9639-9650. doi: 10.2147/OTT.S215400. eCollection 2019.
Membrane-associated guanylate kinase (MAGUK) with inverted orientation protein 1 (MAGI1) is a novel member of the MAGUK family with a vital role in tumor progression related to invasion and metastasis. However, the function of MAGI1 in glioma is currently unknown. We therefore analyzed the expression of MAGI1 protein in human glioma samples, glioma cell lines and glioma stem cells (GSCs), and explored its effects on glioma cell proliferation and apoptosis.
MAGI1 expression in glioma tissues was examined by Western blotting and real-time polymerase chain reaction and its relationships with clinical pathological features were analyzed. The effects of MAGI1 knockdown on the proliferation of glioma cell lines and GSCs were detected by CCK8 and colony-formation assays, and apoptosis was assessed by flow cytometry. We also investigated the effects of MAGI1 silencing on protein expression levels of epithelial-mesenchymal transition biomarkers, as well as β-catenin, cyclin D1, PTEN and phospho-Akt by Western blotting.
MAGI1 was significantly downregulated in glioma tissues and its expression was related to cancer progression. Silencing of MAGI1 in both glioma cell lines and GSCs enhanced proliferation and inhibited apoptosis. MAGI1 knockdown also significantly increased the expression levels of N-cadherin, vimentin, β-catenin, cyclin D1 and phospho-Akt and reduced the expression of E-cadherin and PTEN.
Our results indicated that MAGI1 might play a vital role in glioma progression and may represent a potential therapeutic target for the treatment of glioma.
反向定位膜相关鸟苷酸激酶(MAGUK)蛋白1(MAGI1)是MAGUK家族的一个新成员,在与侵袭和转移相关的肿瘤进展中起重要作用。然而,MAGI1在胶质瘤中的功能目前尚不清楚。因此,我们分析了MAGI1蛋白在人胶质瘤样本、胶质瘤细胞系和胶质瘤干细胞(GSCs)中的表达,并探讨了其对胶质瘤细胞增殖和凋亡的影响。
采用蛋白质免疫印迹法和实时聚合酶链反应检测胶质瘤组织中MAGI1的表达,并分析其与临床病理特征的关系。通过CCK8和集落形成试验检测MAGI1基因敲低对胶质瘤细胞系和GSCs增殖的影响,采用流式细胞术评估细胞凋亡情况。我们还通过蛋白质免疫印迹法研究了MAGI1沉默对上皮-间质转化生物标志物以及β-连环蛋白、细胞周期蛋白D1、PTEN和磷酸化Akt蛋白表达水平的影响。
MAGI1在胶质瘤组织中显著下调,其表达与癌症进展相关。在胶质瘤细胞系和GSCs中沉默MAGI1可增强细胞增殖并抑制细胞凋亡。敲低MAGI1还显著增加了N-钙黏蛋白、波形蛋白、β-连环蛋白、细胞周期蛋白D及磷酸化Akt的表达水平,降低了E-钙黏蛋白和PTEN的表达水平‘
我们的结果表明,MAGI1可能在胶质瘤进展中起重要作用,可能是治疗胶质瘤的潜在靶点。