肺癌是世界上最常见的恶性肿瘤之一。死亡率在各种恶性肿瘤中排名第一。GTP结合蛋白(鸟苷5'-三磷酸结合蛋白,GTPBP)是一种具有信号转导功能的蛋白质,具有GTP水解酶活性,并在细胞信号传输中发挥重要作用,细胞骨架调节,蛋白质合成和其他活动。GTPBP2是G卵白超家族的成员之一。GTPBP2的研究目前主要集中在人类遗传学,其在肿瘤方面的研究尚未见报道。首先,采用Westernblot和实时定量PCR方法分析12例GTPBP2在人NSCLC新鲜癌组织和癌旁组织中的表达差异。然后选取112例NSCLC癌组织和65例癌旁组织进行免疫组化实验,分析GTPBP2的表达与临床病理参数及预后的关系,我们发现GTPBP2在NSCLC癌组织中高表达,GTPBP2的高表达与pTNM分期和淋巴结转移有关。此外,GTPBP2敲低后,GTPBP2可通过上调RhoC和MMP-9促进NSCLC细胞株的增殖和侵袭,上调cyclinD1、CDK4和c-myc,并下调P27以促进NSCLC细胞系的侵袭。此外,GTPBP2负调控Axin促进β-catenin表达,从而激活Wnt/β-连环蛋白信号,促进NSCLC的发生。
Lung cancer is one of the most common malignant tumors in the world, and the mortality rate ranks first among various malignant tumors. GTP-binding proteins (guanosine 5\'-triphosphate-binding proteins, GTPBPs) are a type of protein with signal transduction function, have GTP hydrolase activity, and play an important role in cell signal transmission, cytoskeletal regulation, protein synthesis and other activities.
GTPBP2 is one of the members of the G protein superfamily. Research on GTPBP2 is currently focused on human genetics, and its research in tumors has not been reported. First, Western blot and quantitative real-time PCR were used to analyze the expression differences of 12 cases of GTPBP2 in human NSCLC fresh cancer tissues and adjacent tissues. Then we selected 112 cases of NSCLC cancer tissues and 65 adjacent tissues for immunohistochemistry experiments to analyze the relationships between the expression of GTPBP2 and clinical pathological parameters and prognosis, we found that
GTPBP2 is highly expressed in NSCLC cancer tissues, and the high expression of
GTPBP2 is related to pTNM stage and lymph node metastasis. In addition, after
GTPBP2 knockdown,
GTPBP2 can promote the proliferation and invasion of NSCLC cell lines by up-regulating RhoC and MMP-9, and up-regulate cyclinD1, CDK4 and c-myc, and down-regulate P27 to promote the invasion of NSCLC cell lines. In addition,
GTPBP2 negatively regulates Axin to promote β-catenin expression, thereby activating Wnt/β-catenin signaling, and promoting the occurrence of NSCLC.