Cyclin B1 stability is increased by interaction with BRCA1, and its overexpression suppresses the progression of BRCA1-associated mammary tumors

Choi, Eun Kyung; Lim, Joong‐Soo; Kim, Jong Kwang; Jang, Mi; Kim, Sun Eui; Baek, Hye Jung; Park, Eun Jung; Kim, Tae Hyun; Deng, Chu‐Xia; Wang, Ruihong; Kim, Sang Soo

doi:10.1038/s12276-018-0169-z

Cited by 11 publications

(8 citation statements)

References 39 publications

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“…Previous studies have implicated the role of Cyclin B1 in the regulation of cell proliferation in breast cancer. [35][36][37] In our study, the results indicated that Aurora A-Cyclin B1 axis plays a crucial role in obesity breast cancer. The degree of heterogeneity and the expression pattern of biomarkers under study may constitute a potential problem in tissue microarray-based study.…”

Section: Dovepresssupporting

confidence: 54%

<p>Identification of Aurora Kinase A as a Biomarker for Prognosis in Obesity Patients with Early Breast Cancer</p>

Jiang¹,

Guo²,

Xu³

et al. 2020

OTT

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Background: Obesity is associated both with a higher risk of developing breast cancer, particularly in postmenopausal women, and with worse disease outcome for women of all ages. Previous investigation suggested Aurora A kinase was able to partially restore the functionalities of obese adipose-derived mesenchymal stem cells by stabilizing their primary cilia and reestablishing a balance of multiple stemness-associated genes. The association between Aurora A and obesity breast cancer is still unclear. We hypothesized that overexpression of Aurora A was associated with poor survival in obesity breast cancer and the related axis mechanism was involved. Methods: A total of 517 primary breast cancer specimens were collected from the First Affiliated Hospital of China Medical University between January 2011 and November 2016. Our independent variable was BMI at baseline, categorized as overweight (BMI ≥25 kg/m 2 , as obesity cohort), and normal (18.5 ≤ BMI <25 kg/m 2 , as non-obesity cohort). The immunohistochemical (IHC) staining was performed with Aurora A, Survivin, MMP11, Cyclin B1, and Cathepsin L. Kaplan-Meier curve was used to analyze overall survival in our cohorts and TCGA-BRCA data (GSE3494). Log rank test was used to calculate P values. Protein-protein interaction (PPI) network analysis and MCODE model were used to analyze the Aurora-altered signal pathway from GSE78958. Results: Among 517 breast patients, Aurora A-positive (staining scores ≥4) was significantly higher in obesity breast carcinoma compared with non-obesity cancer carcinoma (χ 2 =9.79, P=0.002), with more frequency in hormone receptor-negative (68.4% vs 77.9%, P=0.015) and HER2-positive patients (28.7% vs 17.9%, P=0.003). High Aurora A expression was remarkably and significantly associated with overall survival (OS) (8-year OS ratio: 69.5% vs 81.1%, OR=1.76, 95% CI: 1.03~3.02, P=0.041) in obesity cohort. Interestingly, higher expression of Aurora A was not associated with a shorter overall survival time among the non-obesity breast cancer (8-year OS ratio: 81.4% vs 85.8%, OR=1.40, 95% CI: 0.79~2.45, P=0.229). As for RFS, the expression levels of Aurora A expression genes have no significance with RFS statistically in nonobesity and obesity patients. Aurora A and lymph node metastases were significantly poor prognostic factors for OS, and borderline significance was noted for high BMI. Kaplan-Meier survival analysis from TCGA database confirmed that the high Aurora A expression group had worse prognosis (HR=1.47, 95% CI: 1.14-1.90, P=0.003). The KEGG pathway enrichment results were consistent with GO biological process term analysis, in which CCNB1 was enriched for upregulated Aurora A. In our samples, Aurora A level on tumor cytoplasm had broad connections with Cyclin B1 by IHC correlation analysis (correlation coefficient = 0.227, P=0.001). Conclusion: Our finding demonstrates here for the first time that high expression of Aurora A was notably correlated with early recurrence and poor overall survival in obesity patients with early breast ca...

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Section: Dovepresssupporting

confidence: 54%

<p>Identification of Aurora Kinase A as a Biomarker for Prognosis in Obesity Patients with Early Breast Cancer</p>

Jiang¹,

Guo²,

Xu³

et al. 2020

OTT

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“…Freitas et al (2016) thought hierridin B was a potential anticancer compound that targeted CCNB1. A study in breast cancer confirmed that targeting CCNB1 was useful in BRCA1-associated breast cancer therapy (Choi et al, 2018). In clinical, Resveratrol (Joe et al, 2002), quercetin (Choi et al, 2001), and genistein (Wiseman et al, 2007) were the representative targeted drugs.…”

Section: Discussionmentioning

confidence: 94%

Identification of Hub Genes Associated With Progression and Prognosis in Patients With Bladder Cancer

Yan

Guo

et al. 2019

Front. Genet.

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Given that most bladder cancers (BCs) are diagnosed in advanced stages with poor prognosis, this study aims to find novel biomarkers associated with the progression and prognosis in patients with BC. 1,779 differentially expressed genes (DEGs) between BC samples and normal bladder tissues were identified in total. Then, 24 DEGs were regarded as candidate hub genes by constructing a protein–protein interaction (PPI) network and a random forest model. Among them, six genes (BUB1B, CCNB1, CDK1, ISG15, KIF15, and RAD54L) were eventually identified by using five analysis methods (one-way Analysis of Variance analysis, spearman correlation analysis, distance correlation analysis, receiver operating characteristic curve, and expression values comparison), which were correlated with the progression and prognosis of BC. Moreover, the validation of hub genes was conducted based on GSE13507, Oncomine, and CBioPortal. Results of univariate Cox regression analysis showed that the expression levels of all the hub genes were influence features of overall survival (OS) and cancer specific survival (CSS) based on GSE13507, and we further established a six-gene signature based on the expression levels of the six genes and their Cox regression coefficients. This signature showed good potential for clinical application suggested by survival analysis (OS: Hazard Ratio = 0.484, 95%CI: 0.298–0.786; P = 0.0034; CSS: Hazard Ratio = 0.244, 95%CI: 0.121–0.493, P < 0.0001) and decision curve analysis. In conclusion, our study indicates that six hub genes have great predictive value for the prognosis and progression of BC and may contribute to the exploration of further basic and clinical research of BC.

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“…Treszezamsky et al found that BRCA1-and BRCA2-deficient cells are sensitive to Etoposide, which targeting topoisomerase II (TOP2A) and inducing DNA double-strand breaks [27]. High expression of CCNB1 was also observed in BRCA1-mutant cancer and induction of vinblastine targeting CCNB1 could significantly reduce tumor progression [28]. BRCA2 could interact with Filamin A actin-binding protein, further recruiting endosomal sorting complex required for transport (ESCRT)-associated proteins, Alix and Tsg101, and forming CEP55-Alix and CEP55-Tsg101 complexes at the midbody.…”

Section: Discussionmentioning

confidence: 99%

Construction of a novel prognostic-predicting model correlated to ovarian cancer

Tang

Chang

et al. 2020

Bioscience Reports

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Background: Ovarian cancer (OC) is one of the most lethal gynecological cancers worldwide. The pathogenesis of the disease and outcomes prediction of ovarian cancer patients remain largely unclear. This study aimed to explore the key genes and biological pathways in ovarian carcinoma development, as well as construct a prognostic model to predict patients’ overall survival. Results: We identified 164 up-regulated and 80 down-regulated differentially-expressed genes (DEGs) associated with ovarian cancer. GO term enrichment showed DEGs mainly correlated with spindle microtubes. For KEGG pathways, cell cycle was mostly enriched for the DEGs. The PPI network yielded 238 nodes and 1284 edges. Top three modules and 10 hub genes were further filtered and analyzed. Three candidiate drugs targeting for therapy were also selected. Thirteen OS-related genes were selected and an eight-mRNA model was present to stratify patients into high- and low-risk groups with significantly different survival. Conclusions: The identified DEGs and biological pathways may provide new perspective on the pathogenesis and treatments of OC. The identified 8-mRNA signature has significant clinical implication for outcome prediction and tailored therapy guidance for OC patients.

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Cyclin B1 stability is increased by interaction with BRCA1, and its overexpression suppresses the progression of BRCA1-associated mammary tumors

Cited by 11 publications

References 39 publications

<p>Identification of Aurora Kinase A as a Biomarker for Prognosis in Obesity Patients with Early Breast Cancer</p>

<p>Identification of Aurora Kinase A as a Biomarker for Prognosis in Obesity Patients with Early Breast Cancer</p>

Identification of Hub Genes Associated With Progression and Prognosis in Patients With Bladder Cancer

Construction of a novel prognostic-predicting model correlated to ovarian cancer

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