Abstract
BackgroundThe 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.MethodsThis 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.ResultsHerein, 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.ConclusionsTaken 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.
Highlights
The sperm-associated antigen 5 (SPAG5) plays a key role in controlling various cellular phenomena, including cell cycle progression and proliferation
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-Scavenger receptor class A member 5 (SCARA5) might be a novel pathway involved in hepatocellular carcinoma (HCC) progression
SPAG5 is significantly upregulated in HCC tissues and cells To identify the potential roles of SPAG5 in the development and progression of hepatocellular carcinoma, we first examined SPAG5 expression in 136 hepatocellular carcinoma (HCC) tissue samples and corresponding adjacent tissues by qRT-polymerase chain reaction (PCR)
Summary
The sperm-associated antigen 5 (SPAG5) plays a key role in controlling various cellular phenomena, including cell cycle progression and proliferation. The role of SPAG5 in hepatocellular carcinoma (HCC) remains unknown. Despite current advances in the diagnosis of HCC, the majority of patients are not eligible for surgical treatment due to late diagnosis. The five-year survival rate of patients undergoing surgical resection is disappointingly low [3]. Tumor proliferation and apoptosis plays an important role in the occurrence and development of HCC [4]. The researches have demonstrated that HCC proliferation and apoptosis are closely related to abnormal expression of oncogenes and tumor suppressor genes [5, 6]. Identification of novel diagnostic markers and therapeutic targets in HCC are urgently needed
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