SGOL2 is a novel prognostic marker and fosters disease progression via a MAD2-mediated pathway in hepatocellular carcinoma

被引:6
作者
Hu, Qingqing [1 ]
Liu, Qiuhong [1 ]
Zhao, Yalei [1 ]
Zhang, Lingjian [1 ]
Li, Lanjuan [1 ]
机构
[1] Zhejiang Univ, Collaborat Innovat Ctr Diag & Treatment Infect Di, State Key Lab Diag & Treatment Infect Dis, Natl Clin Res Ctr Infect Dis,Affiliated Hosp 1,Co, Hangzhou 310003, Peoples R China
基金
中国国家自然科学基金; 芬兰科学院;
关键词
SGOL2; MAD2; Cell cycle; Hepatocellular carcinoma; Prognosis; SISTER-CHROMATID COHESION; PROTEIN PHOSPHATASE 2A; CANCER; SHUGOSHIN; ANEUPLOIDY; MAD2; PROLIFERATION; ZBP-89; CELLS; OVEREXPRESSION;
D O I
10.1186/s40364-022-00422-z
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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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页数:18
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共 69 条
[1]   ZBP-89-induced apoptosis is p53-independent and requires JNK [J].
Bai, L ;
Yoon, SO ;
King, PD ;
Merchant, JL .
CELL DEATH AND DIFFERENTIATION, 2004, 11 (06) :663-673
[2]   ZBP-89 promotes growth arrest through stabilization of p53 [J].
Bai, LG ;
Merchant, JL .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (14) :4670-4683
[3]   Sister Chromatid Cohesion Control and Aneuploidy [J].
Barbero, J. L. .
CYTOGENETIC AND GENOME RESEARCH, 2011, 133 (2-4) :223-233
[4]   Targeting transcription factors in cancer - from undruggable to reality [J].
Bushweller, John H. .
NATURE REVIEWS CANCER, 2019, 19 (11) :611-624
[5]   The association between MAD2 and prognosis in cancer: a systematic review and meta-analyses [J].
Byrne, Tara ;
Coleman, Helen G. ;
Cooper, Janine A. ;
McCluggage, W. Glenn ;
McCann, Amanda ;
Furlong, Fiona .
ONCOTARGET, 2017, 8 (60) :102223-102234
[6]   A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers [J].
Carter, Scott L. ;
Eklund, Aron C. ;
Kohane, Isaac S. ;
Harris, Lyndsay N. ;
Szallasi, Zoltan .
NATURE GENETICS, 2006, 38 (09) :1043-1048
[7]  
Chen Q, 2019, AM J CANCER RES, V9, P2693
[8]  
Corbett KD, 2017, PROG MOL SUBCELL BIO, V56, P429, DOI 10.1007/978-3-319-58592-5_18
[9]   Cumulative Haploinsufficiency and Triplosensitivity Drive Aneuploidy Patterns and Shape the Cancer Genome [J].
Davoli, Teresa ;
Xu, Andrew Wei ;
Mengwasser, Kristen E. ;
Sack, Laura M. ;
Yoon, John C. ;
Park, Peter J. ;
Elledge, Stephen J. .
CELL, 2013, 155 (04) :948-962
[10]   The Mad1/Mad2 complex as a template for Mad2 activation in the spindle assembly checkpoint [J].
De Antoni, A ;
Pearson, CG ;
Cimini, D ;
Canman, JC ;
Sala, V ;
Nezi, L ;
Mapelli, M ;
Sironi, L ;
Faretta, M ;
Salmon, ED ;
Musacchio, A .
CURRENT BIOLOGY, 2005, 15 (03) :214-225