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SPAG9的过表达与肝细胞癌的不良预后和肿瘤进展相关。

Overexpression of SPAG9 correlates with poor prognosis and tumor progression in hepatocellular carcinoma.

作者信息

Xie Chengyao, Fu Lin, Liu Nan, Li Qingchang

机构信息

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Bei'er Road 92, Heping District Shenyang, 110001, Liaoning, People's Republic of China,

出版信息

Tumour Biol. 2014 Aug;35(8):7685-91. doi: 10.1007/s13277-014-2030-x. Epub 2014 May 8.

Abstract

Sperm-associated antigen 9 (SPAG9) was reported as a novel biomarker for several cancers and associated with the malignant behavior of cancer cells. However, its expression pattern and biological role in human hepatocellular carcinoma (HCC) have not been reported. In the present study, we analyzed SPAG9 expression in human HCC tissues by immunohistochemistry and found that SPAG9 overexpression is correlated with tumor stage (p < 0.001), tumor multiplicity (p = 0.019), tumor size (p = 0.034), AFP levels (p = 0.006), and tumor relapse (p = 0.0017). Furthermore, SPAG9 overexpression is correlated with poor overall survival (p < 0.001) and relapse-free survival (p = 0.002). Transfection of SPAG9 small interfering RNA (siRNA) was performed in Bel-7402 cell line. Colony formation and MTT showed that SPAG9 siRNA knockdown inhibited HCC cell proliferation. We also found that SPAG9 depletion could increase cell apoptosis. In addition, the level of cyclin D1 and cyclin E protein expression was downregulated after siRNA treatment. In conclusion, SPAG9 is overexpressed in human HCC and serves as a prognostic marker. SPAG9 contributes to cancer cell growth through regulation of cyclin proteins.

摘要

精子相关抗原9(SPAG9)被报道为多种癌症的新型生物标志物,并与癌细胞的恶性行为相关。然而,其在人类肝细胞癌(HCC)中的表达模式和生物学作用尚未见报道。在本研究中,我们通过免疫组织化学分析了人类HCC组织中SPAG9的表达,发现SPAG9过表达与肿瘤分期(p < 0.001)、肿瘤多灶性(p = 0.019)、肿瘤大小(p = 0.034)、甲胎蛋白水平(p = 0.006)以及肿瘤复发(p = 0.0017)相关。此外,SPAG9过表达与总体生存率低(p < 0.001)和无复发生存率低(p = 0.002)相关。在Bel - 7402细胞系中进行了SPAG9小干扰RNA(siRNA)转染。集落形成和MTT实验表明,SPAG9 siRNA敲低抑制了HCC细胞增殖。我们还发现,SPAG9缺失可增加细胞凋亡。此外,siRNA处理后细胞周期蛋白D1和细胞周期蛋白E蛋白表达水平下调。总之,SPAG9在人类HCC中过表达,可作为一种预后标志物。SPAG9通过调节细胞周期蛋白促进癌细胞生长。

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