SPC25 overexpression promotes tumor proliferation and is prognostic of poor survival in hepatocellular carcinoma

Zhang, Baozhu; Zhou, Qing; Xie, Qiankun; Lin, Xia; Miao, Wenqiang; Wei, Zhaoguang; Zheng, Tingting; Pang, Zhigang; Liu, Haosheng; Chen, Xi

doi:10.18632/aging.202329

Cited by 12 publications

(13 citation statements)

References 38 publications

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“…The protein encoded by SPC25 was involved in kinetochore-microtubule interaction and spindle checkpoint function. Previous studies have shown that SPC25 upregulation increases CSCs properties and predicted poor prognosis in lung adenocarcinoma, breast cancer, hepatocellular carcinoma and head and neck cancer [46][47][48][49][50].In this study, we innovatively found that SPC25 was highly related to COAD stem cell properties. No studies have found the role of SPC25 in colon cancer.…”

Section: Discussionmentioning

confidence: 68%

Weighted Gene Coexpression Network Analysis of Key Genes Controlling Cancer Stem Cell Characteristics by Mrnasi in Colon Adenocarcinoma

Zhang

Yin

Tong

2021

Preprint

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Background: Cancer stem cells are hidden tumor cells with the potential for self-renewal and multi-differentiation, which are the principal cause of tumor heterogeneity, metastasis and drug resistance. However, the key genes that maintain cell stemness of colon adenocarcinoma (COAD) are still unknown. Our study was designed to identify key genes associated with the stemness of COAD cell. Methods: RNA sequencing data and clinical information were downloaded from The Cancer Genome Atlas (TCGA). Weighted gene coexpression network analysis (WGCNA) was used to recognize key genes based on mRNAsi. Next, the gene expression data downloaded from Gene Expression Omnibus (GEO), Oncomine, and Gene Expression Profiling Integrative Analysis (GEPIA) were used to demonstrate the expression of key genes.Results: The mRNAsi score of COAD tissue was obviously superior than that of normal tissue. N stages, M stages and overall survival were highly related to mRNAsi. WGCNA showed that the green module was positively related to mRNAsi. We obtained 27 genes closely related to each other at the transcriptional and protein levels. The main biological functions of key genes were organelle fission, chromosomal region, and protein serine/threonine kinase activity. The enriched signaling pathway were cell cycle, progesterone−mediated oocyte maturation, human T−cell leukemia virus 1 infection, oocyte meiosis, DNA replication, cellular senescence, viral carcinogenesis, and p53 signaling pathway. The key genes were highly expressed in COAD and various cancers, which was validated multiple databases. Conclusions: 27 key genes were well correlated with maintaining stemness of COAD, which were significantly related to cell cycle events. The key genes may be therapeutic targets for inhibiting the properties of COAD stem cells.

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Section: Discussionmentioning

confidence: 68%

Weighted Gene Coexpression Network Analysis of Key Genes Controlling Cancer Stem Cell Characteristics by Mrnasi in Colon Adenocarcinoma

Zhang

Yin

Tong

2021

Preprint

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“…The present study has mainly focused on the role of spindle pole body component 25 homolog (SPC25) in promoting metastasis in hepatocellular carcinoma (HCC), and in the underlying mechanism. Previous studies have shown that SPC25 is able to promote HCC proliferation, and that it was found to be a prognostic indicator of poor survival in patients with HCC (18)(19)(20). However, these studies were mainly based on bioinformatics analysis, and relevant experimental studies have found only an in vitro phenomenon.…”

Section: Discussionmentioning

confidence: 99%

“…SPC25 has been shown to be highly expressed in tumors, including prostate, breast and non-small cell lung cancer (NSCLC), and is associated with tumor progression (15)(16)(17). In previously published studies on HCC, the results revealed that SPC25 acts as an oncogene in HCC progression (18)(19)(20). However, the underlying mechanism has yet to be fully elucidated.…”

Section: Spc25 Promotes Hepatocellular Carcinoma Metastasis Via Activ...mentioning

confidence: 99%

SPC25 promotes hepatocellular carcinoma metastasis via activating the FAK/PI3K/AKT signaling pathway through ITGB4

2022

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Hepatocellular carcinoma (HCC) is a malignant tumor with a high metastatic rate. Recent studies have shown that the mitosis-associated spindle-assembly checkpoint regulatory protein spindle pole body component 25 homolog (SPC25) promotes HCC progression, although the underlying mechanism has yet to be fully elucidated. The aim of the present study was to investigate the mechanism through which SPC25 may promote HCC progression in greater detail. First, the expression of SPC25 was analyzed in publicly available databases to explore the association between SPC25 and HCC metastasis. Western blotting was subsequently performed to examine the level of SPC25 expression in different HCC cell lines. SPC25 was then silenced in HCCLM3 and Huh7 cells, and the effects of SPC25 silencing were investigated using cell proliferation, wound-healing, Transwell migration assays and an in vivo mouse model. Finally, the mechanism of SPC25 action with respect to the promotion of HCC metastasis was explored using microarray analysis and rescue experiments. The results obtained demonstrated that SPC25 is highly expressed in HCC, and this high level of expression is associated with poor prognosis and metastasis. Moreover, SPC25 silencing led to a marked inhibition of the invasion and migration of HCC cells both in vitro and in vivo. The gene-expression profiling and mechanistic experiments suggest that SPC25 preferentially influences the expression of genes associated with extracellular matrix (ECM)-integrin interactions, including integrin subunit β4 (ITGB4), an upstream element of the integrin pathway. ITGB4 upregulation partly reversed the decline in cell invasion and migration capacities that resulted from SPC25 silencing. Furthermore, deleting both SPC25 and ITGB4 caused a decrease in the phosphorylation of focal adhesion kinase (FAK), phosphoinositide 3-kinase (PI3K) and AKT, which are downstream elements of the integrin pathway. Taken together, the results of the present study demonstrated the important role of SPC25 as a prognostic indicator and as a promoter of metastasis in HCC, and the underlying mechanism of its action has been partially elucidated, suggesting that SPC25 could be used as a biomarker and as a target for therapeutic intervention in the treatment of HCC.

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“…Upregulation of SPC25 expression levels was reported in prostate, lung, and breast cancer cells, and it significantly promoted the proliferation of these tumor cells [16][17][18][19]22) . SPC25 was engaged in the regulation of cell stemness 18) , proliferation 23) , and EMT 24) . A correlation was previously found between TGF-β1 signaling pathway and SPC25 expression levels 24) .…”

Section: Introductionmentioning

confidence: 99%

Highly Expressed SPC25 Promotes the Stemness, Proliferation and EMT of Oral Squamous Cell Carcinoma Cells via Modulating the TGF-β Signaling Pathway

Zhang

Zeng

Xie

et al. 2022

J. Hard Tissue Biology.

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Owing to the high incidence of oral squamous cell carcinoma (OSCC), elucidation of its diagnostic and prognostic factors is of great importance. Spindle pole body component 25 (SPC25) is known to play vital roles in different types of cancer. Nevertheless, the role of SPC25 in OSCC has not been elucidated yet. This study aimed to investigate the potential role of SPC25 in OSCC progression via modulating the transforming growth factor beta-1 (TGF-β1) signaling pathway. Data showed that SPC25 was highly expressed in oral cancer tumors and cells, which was associated with staging and poor survival of OSCC patients. Silencing of SPC25 was found to inhibit proliferation, colony formation, stemness, and epithelial-mesenchymal transition (EMT) of HSC-3 cells. Further analysis revealed that SPC25 overexpression promoted proliferation, colony formation, stemness, and EMT of OCEM-1 cells. In vivo analysis showed that silencing of SPC25 reduced tumor size, volume, and weight; it also suppressed the expression levels of Ki27, CDK2, vimentin, and TGF-β1. Our findings indicated that SPC25 is crucial for the progression of OSCC, and it modulates proliferation, stemness, and EMT of OSCC cells via regulating the TGF-β1 signaling pathway and its associated proteins. This study provided novel insights into the role of SPC25 in the pathogenesis of OSCC, and SPC25 could be a potential therapeutic target for the treatment of OSCC.

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SPC25 overexpression promotes tumor proliferation and is prognostic of poor survival in hepatocellular carcinoma

Cited by 12 publications

References 38 publications

Weighted Gene Coexpression Network Analysis of Key Genes Controlling Cancer Stem Cell Characteristics by Mrnasi in Colon Adenocarcinoma

Weighted Gene Coexpression Network Analysis of Key Genes Controlling Cancer Stem Cell Characteristics by Mrnasi in Colon Adenocarcinoma

SPC25 promotes hepatocellular carcinoma metastasis via activating the FAK/PI3K/AKT signaling pathway through ITGB4

Highly Expressed SPC25 Promotes the Stemness, Proliferation and EMT of Oral Squamous Cell Carcinoma Cells via Modulating the TGF-β Signaling Pathway

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