Journal
BIOMARKER RESEARCH
Volume 10, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s40364-022-00422-z
Keywords
SGOL2; MAD2; Cell cycle; Hepatocellular carcinoma; Prognosis
Categories
Funding
- Key Research and Development Project of the Department of Science and Technology of Zhejiang Province [2017C03051]
- Science Fund for Creative Research Groups of the National Natural Science Foundation of China [81721091]
- Scientific Research Fund of Zhejiang Provincial Education Department [Y202045600]
- Academic Rising Star for Doctoral Candidates of Zhejiang University [202051]
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This study reveals that SGOL2 acts as an oncogene in hepatocellular carcinoma (HCC) by regulating MAD2 and dysregulating the cell cycle, providing a potential therapeutic target for HCC.
Background Shugoshin-like protein 2 (SGOL2) is a centromeric protein that ensures the correct and orderly process of mitosis by protecting and maintaining centripetal adhesions during meiosis and mitosis. Here, we examined the potential role of SGOL2 in cancers, especially in hepatocellular carcinoma (HCC). Methods One hundred ninety-nine normal adjacent tissues and 202 HCC samples were collected in this study. Human HCC cells (SK-HEP-1 and HEP-3B) were employed in the present study. Immunohistochemistry, immunofluorescence, western blot, Co-Immunoprecipitation technique, and bioinformatic analysis were utilized to assess the role of SGOL2 in HCC development process. Results Overexpression of SGOL2 predicted an unfavorable prognosis in HCC by The Cancer Genome Atlas database (TCGA), which were further validated in our two independent cohorts. Next, 47 differentially expressed genes positively related to both SGOL2 and MAD2 were identified to be associated with the cell cycle. Subsequently, we demonstrated that SGOL2 downregulation suppressed the malignant activities of HCC in vitro and in vivo. Further investigation showed that SGOL2 promoted tumor proliferation by regulating MAD2-induced cell-cycle dysregulation, which could be reversed by the MAD2 inhibitor M2I-1. Consistently, MAD2 upregulation reversed the knockdown effects of SGOL2-shRNA in HCC. Moreover, we demonstrated that SGOL2 regulated MAD2 expression level by forming a SGOL2-MAD2 complex, which led to cell cycle dysreuglation of HCC cells. Conclusion SGOL2 acts as an oncogene in HCC cells by regulating MAD2 and then dysregulating the cell cycle, providing a potential therapeutic target in HCC.
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