Overexpression of TIP30 inhibits the growth and invasion of glioma cells.
Overexpression of TIP30 inhibits the growth and invasion of glioma cells.
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TIP30过表达抑制胶质瘤细胞的生长和侵袭
DOI：
10.3892/mmr.2015.4619
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发表时间：
2016-01
影响因子：
3.4
通讯作者：
Luo R
中科院分区：
文献类型：
--
作者：
Hu Y;Chen F;Liu F;Liu X;Huang N;Cai X;Sun Y;Li A;Luo R
脑胶质瘤是一种侵袭性的恶性肿瘤，治疗效果有限，预后差。因此，寻找新的预后标志物和有效的治疗靶点对胶质瘤的治疗具有重要意义。TIP 30是一种肿瘤抑制因子，参与多种细胞过程的调节，包括各种人类癌症中的肿瘤细胞生长、转移和血管生成。本研究旨在探讨Tat相互作用蛋白（TIP）30是否能够调控胶质瘤的发生并预测其临床预后。对92例人脑胶质瘤组织和10例正常脑组织进行免疫组化染色。结果表明，TIP 30在胶质瘤组织中的表达水平显著降低。与正常脑组织样本相比。此外，TIP 30表达与肿瘤组织学分类、病理分级、肿瘤大小和表皮生长因子受体（EGFR）表达呈负相关;然而，TIP 30表达与患者年龄和性别之间没有相关性。此外，与TIP 30阴性表达的患者相比，TIP 30阳性表达的患者表现出显著更长的中位总生存率。体外实验显示，通过慢病毒载体转染上调TIP 30表达抑制细胞生长并诱导细胞凋亡，如分别通过MTT法和Annexin V-异硫氰酸荧光素染色所确定的。此外，TIP 30表达显着减弱细胞迁移和侵袭，如伤口愈合和transwell测定。胶质瘤细胞中TIP 30表达的上调降低了EGFR及其相关下游分子磷酸化细胞外信号调节激酶（ERK）和磷酸化AKT的表达水平，如通过蛋白质印迹分析所确定的。本研究结果表明，TIP 30可以抑制肿瘤发生和胶质瘤进展，从而改善胶质瘤患者的预后。因此，TIP 30可能被证明是有用的预后生物标志物，并作为胶质瘤治疗的潜在靶点。
Glioma is an aggressive malignancy with limited effective treatment and poor prognosis. Therefore, the identification of novel prognostic markers and effective therapeutic targets is important for the treatment of human glioma. TIP30 is a tumor suppressor involved in the regulation of numerous cellular processes, including tumor cell growth, metastasis, and angiogenesis in various human cancers. The present study investigated whether Tat-interacting protein (TIP)30 was able to regulate tumorigenesis and predict the clinical outcome of patients with glioma. A total of 92 human glioma tissue samples and 10 normal brain tissue samples were examined by immunostaining. The results indicated that the expression levels of TIP30 significantly decreased in glioma tissue samples. as compared with normal brain tissue samples. Furthermore, TIP30 expression was inversely correlated with tumor histological classification, pathological grade, tumor size, and epidermal growth factor receptor (EGFR) expression; however, no association was detected between TIP30 expression and patient age and gender. In addition, patients with positive TIP30 expression exhibited significantly longer median overall survival rates, as compared with those with negative TIP30 expression. In vitro experiments revealed that upregulation of TIP30 expression by lentiviral vector transfection inhibited cell growth and induced cell apoptosis, as determined by MTT assay and Annexin V-fluorescein isothiocyanate staining, respectively. In addition, TIP30 expression markedly attenuated cell migration and invasion, as determined by wound healing and transwell assays. Upregulation of TIP30 expression in glioma cells decreased the expression levels of EGFR and its associated downstream molecules phosphorylated extracellular signal-regulated kinases (ERK) and phosphorylated AKT, as determined by western blot analysis. The results of the present study indicated that TIP30 may suppress oncogenesis and glioma progression, thereby improving the prognosis of patients with glioma. Therefore, TIP30 may prove useful as a prognostic biomarker, and as a potential target for glioma therapy.