Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1 Min De Road, Nanchang, 330006, Jiangxi Province, China.
Department of Hepatobiliary Surgery, Tumor Hospital of Guanxi Medical University, Nanning, China.
J Exp Clin Cancer Res. 2018 Sep 18;37(1):229. doi: 10.1186/s13046-018-0891-3.
The sperm-associated antigen 5 (SPAG5) plays a key role in controlling various cellular phenomena, including cell cycle progression and proliferation. However, the role of SPAG5 in hepatocellular carcinoma (HCC) remains unknown.
This study investigated the function and clinical significance of SPAG5 protein expression in hepatocellular carcinoma. We analyzed SPAG5 expression in surgical specimens from 136 HCC patients. The correlation between the clinical characteristics and prognosis was also determined. Furthermore, the SPAG5 was overexpressed in HCC cell and silenced with shRNA in HCC cells. Moreover, cell proliferation and apoptosis were measured using Edu assay and flow cytometry and a molecular mechanism of SPAG5 promotes HCC progression was explored.
Herein, our study showed that upregulation of SPAG5 was detected frequently in primary HCC tissues, and was associated with significantly worse survival among the HCC patients. Multivariate analyses revealed that high SPAG5 expression was an independent predictive marker for the poor prognosis of HCC. SPAG5 silence effectively abolished the proliferation abilities of SPAG5 in vivo and in vitro, while induced apoptosis in HCC cells. Furthermore, our results indicate that SPAG5 promoted cell progression by decreasing SCARA5 expression, which has been reported to control the progression of HCC, and our data demonstrated that SCARA5 is crucial for SPAG5-mediated HCC cell progression in vitro and in vivo. Moreover, we found that the expression of SPAG5 and SCARA5 are inversely correlated in HCC tissues. In addition, we demonstrated that SPAG5 promoted progression in HCC via downregulating SCARA5 depended on the β-catenin/TCF4 signaling pathway. Interestingly, the underlying mechanism is which SPAG5 regulates SCARA5 expression by modulating β-catenin degradation.
Taken together, our data provide a novel evidence for the biological and clinical significance of SPAG5 as a potential biomarker, and we demonstrate that SPAG5-β-catenin-SCARA5 might be a novel pathway involved in HCC progression.
精子相关抗原 5（SPAG5）在控制多种细胞现象中起着关键作用，包括细胞周期进程和增殖。然而，SPAG5 在肝细胞癌（HCC）中的作用尚不清楚。
本研究探讨了 SPAG5 蛋白在肝细胞癌中的功能和临床意义。我们分析了 136 例 HCC 患者手术标本中的 SPAG5 表达。还确定了 SPAG5 表达与临床特征和预后的相关性。此外，在 HCC 细胞中过表达 SPAG5 并在 HCC 细胞中用 shRNA 沉默 SPAG5。此外，使用 Edu 测定和流式细胞术测量细胞增殖和凋亡，并探讨了 SPAG5 促进 HCC 进展的分子机制。
在此，我们的研究表明，SPAG5 在原发性 HCC 组织中经常上调，并且与 HCC 患者的生存率显著降低有关。多变量分析显示，高 SPAG5 表达是 HCC 预后不良的独立预测标志物。SPAG5 沉默有效地消除了 SPAG5 在体内和体外的增殖能力，同时诱导了 HCC 细胞凋亡。此外，我们的结果表明，SPAG5 通过降低已报道控制 HCC 进展的 SCARA5 表达来促进细胞进展，我们的数据表明，SCARA5 对于 SPAG5 介导的 HCC 细胞在体外和体内的进展至关重要。此外，我们发现 SPAG5 和 SCARA5 在 HCC 组织中的表达呈负相关。此外，我们证明 SPAG5 通过下调 SCARA5 依赖于 β-连环蛋白/TCF4 信号通路促进 HCC 的进展。有趣的是，潜在的机制是 SPAG5 通过调节 β-连环蛋白降解来调节 SCARA5 表达。
综上所述，我们的数据为 SPAG5 作为潜在生物标志物的生物学和临床意义提供了新的证据，并证明 SPAG5-β-连环蛋白-SCARA5 可能是参与 HCC 进展的新途径。
