SPAG5 promotes hepatocellular carcinoma progression by downregulating SCARA5 through modifying β-catenin degradation.

BACKGROUND:The sperm-associated antigen 5 plays a key role in controlling various cellular phenomena, including cell cycle progression and proliferation. However, the role of in hepatocellular carcinoma (HCC) remains unknown. METHODS:This study investigated the function and clinical significance of duanyu1842G5 protein expression in hepatocellular carcinoma. We analyzed duanyu1842G5 expression in surgical specimens from 136 HCC patients. The correlation between the clinical characteristics and prognosis was also determined. Furthermore, the duanyu1842G5 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 duanyu1842G5 promotes HCC progression was explored. RESULTS:Herein, our study showed that upregulation of duanyu1842G5 was detected frequently in primary HCC tissues, and was associated with significantly worse survival among the HCC patients. Multivariate analyses revealed that high duanyu1842G5 expression was an independent predictive marker for the poor prognosis of HCC. duanyu1842G5 silence effectively abolished the proliferation abilities of duanyu1842G5 in vivo and in vitro, while induced apoptosis in HCC cells. Furthermore, our results indicate that duanyu1842G5 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 HCC cell progression in vitro and in vivo. Moreover, we found that the expression of duanyu1842G5 and SCARA5 are inversely correlated in HCC tissues. In addition, we demonstrated that duanyu1842G5 promoted progression in HCC via downregulating SCARA5 depended on the β-catenin/TCF4 signaling pathway. Interestingly, the underlying mechanism is which duanyu1842G5 regulates SCARA5 expression by modulating β-catenin degradation. CONCLUSIONS:Taken together, our data provide a novel evidence for the biological and clinical significance of duanyu1842G5 as a potential biomarker, and we demonstrate that might be a novel pathway involved in HCC progression.

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