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Downregulation of SLC5A8 inhibits hepatocellular carcinoma progression through regulation of Wnt/β-catenin signaling

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Tumor Biology

Abstract

SLC5A8 has been shown to be associated with a large number of cancer progressions. However, the biological functions of SLC5A8 in hepatocellular carcinoma (HCC) remain largely unclear. Therefore, we performed this research to explore the functions of SLC5A8 in HCC progression. In this study, SLC5A8 protein and mRNA expression were examined by immunohistochemistry and quantitative real-time PCR, respectively, and we found significantly lower expression levels in HCCs than in the corresponding normal liver tissues. Low SLC5A8 expression was significantly correlated with the clinicopathological features of HCC patients. Patients with low SLC5A8 expression have a shorter overall survival time. This interpretation is confirmed by the results obtained from our in vitro experiments; functional assays indicated that overexpression of SLC5A8, by infection with a recombinant plasmid containing SLC5A8, significantly suppressed HCC cell growth, invasion, and migration and induced HCC cell apoptosis. Moreover, the expression levels of beta-catenin, cyclin D1, c-Myc, MMP-2, and FAK detected by western blotting were downregulated in SLC5A8-transfected HCC cells compared with control-transfected cells, indicating that SLC5A8 has a tumor-suppressive function that acts by interfering with Wnt/β-catenin signaling in HCC.

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Acknowledgments

This project was supported by the Jiangsu Provincial Natural Science Foundation of China (Grant No. BK20131095).

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Correspondence to Gang Li or Jian-Ping Li.

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Ben-Shun Hu and Shu-Ming Xiong contributed to this paper equally.

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Hu, BS., Xiong, SM., Li, G. et al. Downregulation of SLC5A8 inhibits hepatocellular carcinoma progression through regulation of Wnt/β-catenin signaling. Tumor Biol. 37, 13445–13453 (2016). https://doi.org/10.1007/s13277-016-5170-3

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  • DOI: https://doi.org/10.1007/s13277-016-5170-3

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