Journal of Hepatocellular Carcinoma (Feb 2022)

SLC39A1 Overexpression is Associated with Immune Infiltration in Hepatocellular Carcinoma and Promotes Its Malignant Progression

  • Ma X,
  • Zhuang H,
  • Wang Q,
  • Yang L,
  • Xie Z,
  • Zhang Z,
  • Tan W,
  • Tang C,
  • Chen Y,
  • Shang C

Journal volume & issue
Vol. Volume 9
pp. 83 – 98

Abstract

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Xiaowu Ma,1,2,* Hongkai Zhuang,1,2,* Qingbin Wang,1,2 Lei Yang,1,2 Zhiqin Xie,1,2 Ziyu Zhang,1,2 Wenliang Tan,1,2 Chenwei Tang,1,2 Yajin Chen,1,2 Changzhen Shang1,2 1Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yajin Chen; Changzhen Shang, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China, Tel +86-2034070701, Email [email protected]; [email protected]: Solute carrier family 39 member 1 (SLC39A1) has been identified as a zinc ion transport protein that possesses oncogenic properties in various types of cancers. However, its potential function in hepatocellular carcinoma (HCC) remains unknown. This study aimed to investigate the expression profile and potential mechanisms of SLC39A1 in HCC.Methods: SLC39A1 expression was analyzed using multiple databases. The clinical significance and associated biological pathways of SLC39A1 were investigated using bioinformatics analysis. Potential correlations between SLC39A1 expression and tumor immunity in HCC were also evaluated using single-sample gene set enrichment analysis (GSEA). Sixty paired HCC samples were used to verify the expression pattern of SLC39A1. In vitro studies were performed to investigate the oncogenic effects of SLC39A1 in HCC. Western blot analysis was conducted to further investigate the possible involved signaling pathways.Results: The overexpression of SLC39A1 in HCC was determined by bioinformatics analysis and was confirmed in tissues from our center. SLC39A1 overexpression was also significantly correlated with worse prognosis, advanced TNM stage, and histological grade. GSEA analysis demonstrated that SLC39A1 overexpression was involved in various tumor-related pathways, such as the cell cycle and Wnt signaling pathway. SLC39A1 knockdown repressed the proliferation, invasion, and migration abilities of HCC cells. Furthermore, SLC39A1 knockdown decreased the expression of the tumor progression-related proteins (eg, cyclin D1 and MMP2) and Wnt signaling pathway-related proteins (eg, Wnt3A and β-catenin). In addition, SLC39A1 overexpression may be associated with impaired tumor immunity in HCC, as evidenced by the increased infiltration of Th2 cells and reduced infiltration of cytotoxic cells.Conclusion: These findings preliminarily suggested the crucial effect of SLC39A1 overexpression on HCC tumor progression and immunosuppression, suggesting its potential as a novel prognostic and therapeutic target in HCC.Keywords: SLC39A1, hepatocellular carcinoma, prognosis, Wnt signaling pathway, immune infiltration

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