Identification of CDCA8, DSN1 and BIRC5 in Regulating Cell Cycle and Apoptosis in Osteosarcoma Using Bioinformatics and Cell Biology

Li, Qinwen; Liang, Jie; Chen, Bo

doi:10.1177/1533033820965605

Cited by 9 publications

(9 citation statements)

References 38 publications

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“…High-level expression of CENP-U in the testes may also account for previous results that CENP-U expression was elevated in all tumors compared with matched normal tissues except for TGCT. Our results were also consistent with previous findings that showed CENP-U expression to be increased in BRCA (16,17), GBM (18), PRAD (19), osteosarcoma (20), LIHC (21), BLCA (22), LUAD (23), and OV (24). The differential expression of CENP-U in other tumors warrants further research.…”

Section: Discussionsupporting

confidence: 93%

“…Additionally, CENP-U plus Bub1 was found to recruit PLK1 to kinetochore, which is crucial for stabilizing the proper kinetochore-microtubule attachments and in the accurate distribution of DNA (13,35). Recently, elevated CENP-U expression was identified in a number of cancers (16)(17)(18)(19)(20)(21)(22)(23)(24) and high CENP-U expression was correlated to poor prognosis in BRCA, LIHC, BLCA, and LUAD (16,17,(21)(22)(23). However, the underlying mechanisms remain unclear.…”

Section: Discussionmentioning

confidence: 99%

“…For another, CENP-I was recently reported to promote the proliferation and migration of gastric cancer (GC) and a series of CENP proteins including CENP-U were reported to be upregulated in GC (15). As an important regulator of mitosis, CENP-U was found to be elevated in breast cancer (BRCA) (16,17), glioblastoma multiforme (GBM) (18), prostate adenocarcinoma (PRAD) (19), osteosarcoma (20), liver hepatocellular carcinoma (LIHC) (21), bladder urothelial carcinoma (BLCA) (22), lung adenocarcinoma (LUAD) (23), and ovarian cancer (OV) (24); further, highly expressed CENP-U has been correlated with poor prognosis (16,17,(21)(22)(23). However, the underlying mechanisms of CENP-U in tumor immunity, metabolism, and proliferation are not fully understood, and thus further analysis is needed.…”

Section: Introductionmentioning

confidence: 99%

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Mitosis-related gene CENP-U as a potential biomarker in malignancy

Shao¹,

Wang²,

Duan³

et al. 2021

Ann Transl Med

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Background: Centromere protein U (CENP-U) is a component of the kinetochore and can regulate the cell cycle as a receptor of polo-like kinase 1 (PLK1). Recent studies have partially identified the role of CENP-U in tumor progression, but the underlying mechanisms of CENP-U in tumor immunity remain obscure. Methods: We performed pan-cancer analysis to evaluate the role of CENP-U in immunity and proliferation with data from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE) datasets, and Genotype-Tissue Expression (GTEx) project. Results of CENP-U expression and related clinicopathological data were obtained to show the expression levels, prognosis, tumor progression, immune neoantigens, and immune checkpoints of CENP-U in 33 tumors. The Tumor Immune Estimation Resource (TIMER) dataset was used to analyze immune infiltration scores.Results: Results of the pan-cancer analysis demonstrated that CENP-U is differentially expressed in normal tissues and common tumor tissues. Moreover, differentially expressed CENP-U was also identified between matched normal and tumor tissues, and the high expression level of CENP-U was associated with poor prognosis for 33 kinds of tumor except for that of thymoma (THYM) and lymphoid neoplasm diffuse large B-cell lymphoma (DLBC). Furthermore, the correlation between CENP-U expression and immune checkpoints and immune neoantigens was determined. In addition, CENP-U expression was correlated with tumor-infiltrating immune cells especially in THYM but not in lung squamous cell carcinoma (LUSC), esophageal carcinoma (ESCA), or lung adenocarcinoma (LUAD). Finally, gene set enrichment analysis (GSEA) indicated that CENP-U is critically involved in tumor proliferation, immunity, and metabolism.Conclusions: CENP-U, a mitosis-related kinase, was found to be differentially expressed across different cancer types and to play an important role in tumor progression and immunity. CENP-U holds the potential to be a prognostic marker, whose targeting may provide therapeutic benefit.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mitosis-related gene CENP-U as a potential biomarker in malignancy

Shao¹,

Wang²,

Duan³

et al. 2021

Ann Transl Med

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“…Furthermore, chromosomal instability, which can lead to abnormal chromosome structure and number, is a prominent feature in human cancers [ 37 ]. DSN1 has already been reported to be upregulated and to act as a considerable risk factor in various tumors, and depletion of DSN1 can inhibit the cellular malignant phenotype [ 35 – 38 ]. In our present study, the expression of DSN1 was significantly up-regulated in CRC cells and clinical tissue samples and indicated poor prognosis in CRC patients, suggesting that DSN1 contributes to maintaining the malignant phenotype of CRC.…”

Section: Discussionmentioning

confidence: 99%

SRSF9 promotes colorectal cancer progression via stabilizing DSN1 mRNA in an m6A-related manner

Wang

et al. 2022

J Transl Med

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Background Serine/arginine-rich splicing factor 9 (SRSF9) is a classical RNA-binding protein that is essential for regulating gene expression programs through its interaction with target RNA. Whether SRSF9 plays an essential role in colorectal cancer (CRC) progression and can serve as a therapeutic target is largely unknown. Here, we highlight new findings on the role of SRSF9 in CRC progression and elucidate the underlying mechanism. Methods CRC cell lines and clinical tissue samples were used. qRT-PCR, Western blotting, immunohistochemistry (IHC), gain- and loss-of-function assays, animal xenograft model studies, bioinformatic analysis, methylated single-stranded RNA affinity assays, gene-specific m6A quantitative qRT-PCR, dual-luciferase reporter assays and RNA stability assays were performed in this study. Results The expression level of SRSF9 was higher in CRC cell lines than that in an immortal human intestinal epithelial cell line. Overexpression of SRSF9 was positively associated with lymph node metastasis and Dukes stage. Functionally, SRSF9 promoted cell proliferation, migration and invasion in vitro and xenograft growth. The results of bioinformatic analysis indicated that DSN1 was the downstream target of SRSF9. In CRC cells and clinical tissue samples, the expression of SRSF9 was positively associated with the expression of DSN1. Knockdown of DSN1 partially inhibited the SRSF9-induced phenotype in CRC cells. Mechanistically, we further found that SRSF9 is an m6A-binding protein and that m6A modifications were enriched in DSN1 mRNA in CRC cells. Two m6A modification sites (chr20:36773619–36773620 and chr20:36773645–chr20:36773646) in the SRSF9-binding region (chr20:36773597–36773736) of DSN1 mRNA were identified. SRSF9 binds to DSN1 in an m6A motif- and dose-dependent manner. SRSF9 modulates the expression of DSN1 in CRC cells. Such expression regulation was largely impaired upon methyltransferase METTL3 knockdown. Moreover, knockdown of SRSF9 accelerated DSN1 mRNA turnover, while overexpression of SRSF9 stabilized DSN1 mRNA in CRC cells. Such stabilizing was also weakened upon METTL3 knockdown. Conclusion Overexpression of SRSF9 was associated with lymph node metastasis and Dukes stage in CRC. Knockdown of DSN1 eliminated the effects by SRSF9 overexpression in CRC. Our results indicated that SRSF9 functions as an m6A-binding protein (termed “reader”) by enhancing the stability of DSN1 mRNA in m6A-related manner. Our study is the first to report that SRSF9-mediated m6A recognition has a crucial role in CRC progression, and highlights SRSF9 as a potential therapeutic target for CRC management.

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“…The recent study noted that the high-expression BIRC5 was correlated with low overall survival in lung adenocarcinoma patients, and the overexpression of BIRC5 is a risk factor for a worse prognosis [ 38 ]. Apoptosis repeat protein domain was inhabited by BIRC5 to militate against apoptosis inhibition [ 39 ], and siBIRC5 could overcome the antiapoptosis protection of cisplatin-resistant cells [ 40 ]. As a necessary protein of CPC, BIRC5 is also required for the mitotic exit and plays a major role in the cell cycle [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Anticancer Action of Xiaoxianxiong Tang in Non-Small Cell Lung Cancer by Pharmacological Analysis and Experimental Validation

Ding

Jiao

Sang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Xiaoxianxiong Tang (XXXT) is a well-known traditional Chinese medicine formula. Evidence is emerging supporting the benefits of XXXT in ameliorating therapy for non-small cell lung cancer (NSCLC). The purpose of this study aimed to explore the effects and mechanisms of XXXT through network pharmacological analysis and biological validation. TCMSP database was used to identify potentially active compounds in XXXT with absorption, distribution, metabolism, excretion screening, and their potential targets. The disease targets related to NSCLC were predicted by searching for Therapeutic Target database, GeneCards database, DrugBank database, and DisGeNET database. Of the 4385 NSCLC-related targets, 156 targets were also the targets of compounds present in XXXT. Subsequently, GO function and KEGG pathway enrichment and PPI network analyses revealed that, of the 95 targets and 20 pathways influenced by 20 ingredients in XXXT, 20 targets were associated with patient survival, and XXXT could exert an inhibitory action on the PI3K-AKT signaling pathway. Moreover, XXXT restrained the proliferation of A549 and H460 cells in a concentration-dependent manner and suppressed the mRNA and protein levels of key targets CCNA2, FOSL2, and BIRC5 closely linked to the PI3K-AKT pathway. Hence, XXXT has the potential to improve therapy for NSCLC by targeting the PI3K-AKT signaling pathway.

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Identification of CDCA8, DSN1 and BIRC5 in Regulating Cell Cycle and Apoptosis in Osteosarcoma Using Bioinformatics and Cell Biology

Cited by 9 publications

References 38 publications

Mitosis-related gene CENP-U as a potential biomarker in malignancy

Mitosis-related gene CENP-U as a potential biomarker in malignancy

SRSF9 promotes colorectal cancer progression via stabilizing DSN1 mRNA in an m6A-related manner

Anticancer Action of Xiaoxianxiong Tang in Non-Small Cell Lung Cancer by Pharmacological Analysis and Experimental Validation

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