非小细胞肺癌中富含小谷氨酰胺重复序列和四肽重复蛋白α(SGTA)作为一种新型细胞周期蛋白的表达和临床作用。
Expression and clinical role of small glutamine-rich tetratricopeptide repeat (TPR)-containing protein alpha (SGTA) as a novel cell cycle protein in NSCLC.
机构信息
Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, China.
出版信息
J Cancer Res Clin Oncol. 2013 Sep;139(9):1539-49. doi: 10.1007/s00432-013-1474-5. Epub 2013 Jul 16.
PURPOSE
A small glutamine-rich tetratricopeptide repeat-containing protein alpha (SGTA) is a 35 kDa protein involved in a number of biological processes. However, the role of SGTA in non-small-cell lung cancer (NSCLC) tumorigenesis has never been elucidated. The purpose of this study was to determine whether SGTA could serve as a biomarker for stratification and prediction of prognosis in NSCLC.
METHODS
Small glutamine-rich tetratricopeptide repeat-containing protein alpha expression was evaluated by Western blot in 8 paired fresh lung cancer tissues and immunohistochemistry on 83 paraffin-embedded sections. The effect of SGTA was assessed by RNA interference in A549 cells. Serum starvation and refeeding, flow cytometry, CCK-8, and tunnel assays were performed.
RESULTS
Small glutamine-rich tetratricopeptide repeat-containing protein alpha was highly expressed in NSCLC and significantly correlated with NSCLC histological differentiation, clinical stage, and Ki-67. Multivariate analysis indicated that SGTA was an independent prognostic factor for NSCLC patients' survival. The present investigation demonstrated that suppression of SGTA expression resulted in a significant decline of proliferation in A549 cells. Besides, SGTA could abolish the toxicity of cisplatin in A549 cells.
CONCLUSIONS
These findings suggested that SGTA might play an important role in promoting the tumorigenesis of NSCLC, and thus be a promising therapeutic target to prevent NSCLC progression.
目的
富含小谷氨酰胺的四肽重复蛋白α(SGTA)是一种 35kDa 的蛋白质,参与许多生物过程。然而,SGTA 在非小细胞肺癌(NSCLC)肿瘤发生中的作用尚未阐明。本研究旨在确定 SGTA 是否可以作为 NSCLC 分层和预后预测的生物标志物。
方法
通过 Western blot 在 8 对新鲜肺癌组织中评估 SGTA 的表达,并通过免疫组织化学在 83 个石蜡包埋切片中评估 SGTA 的表达。通过 RNA 干扰在 A549 细胞中评估 SGTA 的作用。进行血清饥饿和再喂养、CCK-8 和隧道实验。
结果
SGTA 在 NSCLC 中高表达,与 NSCLC 的组织学分化、临床分期和 Ki-67 显著相关。多因素分析表明,SGTA 是 NSCLC 患者生存的独立预后因素。本研究表明,抑制 SGTA 表达可导致 A549 细胞增殖显著下降。此外,SGTA 可以消除 A549 细胞中顺铂的毒性。
结论
这些发现表明,SGTA 可能在促进 NSCLC 的肿瘤发生中发挥重要作用,因此可能是预防 NSCLC 进展的有前途的治疗靶点。