Network-Based Approach to Identify the Antiproliferative Mechanisms of Bruceine D in Breast Cancer From the Cancer Genome Atlas

Tian, Sai; Jiang, Rui; Zhang, Weidong

doi:10.3389/fonc.2020.01001

Cited by 6 publications

(3 citation statements)

References 39 publications

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“…Increasing findings support the use of Narciclasine and Bruceine D as antitumor agents [33,46]. Several studies have reported the antitumor mechanisms of the two drugs [47][48][49], but natural products often have multiple molecular targets. Therefore, based on the transcriptome data of 212 breast cell lines treated by different drugs, this study comprehensively explored the underlying antitumor targets for Narciclasine and Bruceine D.…”

Section: Discussionmentioning

confidence: 92%

Bruceine D and Narclasine inhibit the proliferation of breast cancer cells and the prediction of potential drug targets

Chen,

2024

PLoS ONE

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Background Breast cancer is one of the most common female malignancies. This study explored the underlying mechanism through which the two plant compounds (Brucaine D and Narclasine) inhibited the proliferation of breast cancer cells. Objective The purpose of this study was to explore the effect of Brucaine D and Narclasine on breast cancer development and their potential drug targets. Methods GSE85871 dataset containing 212 samples and the hallmark gene set “h.all.v2023.1.Hs.symbols.gmt” were downloaded from the Gene Expression Omnibus (GEO) database and the Molecular Signatures Database (MSigDB) database, respectively. Principal component analysis (PCA) was applied to classify clusters showing similar gene expression pattern. Single sample gene set enrichment analysis (ssGSEA) was used to calculate the hallmark score for different drug treatment groups. The expressions of genes related to angiogenesis, glycolysis and cell cycle were detected. Protein-protein interaction (PPI) network analysis was performed to study the interaction of the hub genes. Then, HERB database was employed to identify potential target genes for Narclasine and Bruceine D. Finally, in vitro experiments were conducted to validate partial drug-target pair. Results PCA analysis showed that the significant changes in gene expression patterns took place in 6 drugs treatment groups (Narciclasine, Bruceine D, Japonicone A, 1beta-hydroxyalatolactone, Britanin, and four mixture drugs) in comparison to the remaining drug treatment groups. The ssGSEA pathway enrichment analysis demonstrated that Narciclasine and Bruceine treatments had similar enriched pathways, for instance, suppressed pathways related to angiogenesis, Glycolysis, and cell cycle, etc.. Further gene expression analysis confirmed that Narciclasine and Bruceine had a strong ability to inhibit these cell cycle genes, and that MYC, CHEK2, MELK, CDK4 and EZH2 were closely interacted with each other in the PPI analysis. Drug target prediction revealed that Androgen Receptor (AR) and Estrogen Receptor 1 (ESR1) were the targets for Bruceine D, and Cytochrome P450 3A4 enzyme (CYP3A4) was the target for Narciclasine. Cell experiments also confirmed the connections between Narciclasine and CYP3A4. Conclusion The present study uncovered that Narciclasine and Bruceine D could inhibit the growth of breast cancer and also predicted the potential targets for these two drugs, providing a new therapeutic direction for breast cancer patients.

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Section: Discussionmentioning

confidence: 92%

Bruceine D and Narclasine inhibit the proliferation of breast cancer cells and the prediction of potential drug targets

Chen,

2024

PLoS ONE

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“…It is anticipated that there would be 405,680 women in China who are at risk for breast cancer by the year 2025. [8][9][10] Breast cancer is the leading cause of BMS, accounting for about 10% to 30% of metastatic breast cancer cases, second only to lung cancer in BMS rate. [11,12] The molecular mechanism of BMS is still unclear.…”

Section: Declarations All Authors Of This Manuscript Have Confirmed T...mentioning

confidence: 99%

“…It is anticipated that there would be 405,680 women in China who are at risk for breast cancer by the year 2025. [8–10]…”

Section: Introductionmentioning

confidence: 99%

Screening and identification of hub-gene associated with brain metastasis in breast cancer

Niu

et al. 2023

Medicine

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Background: The presence of breast cancer in the brain, also known as brain metastasis (BMS), is the primary reason for a bad prognosis in cases of breast cancer. Breast cancer is the most prevalent malignant tumor seen in women in developing nations. At present, there is no effective method to inhibit brain metastasis of breast cancer. Therefore, it is necessary to conduct a systematic study on BMS of breast cancer, which will not provide ideas and sites for follow-up studies on the treatment and inhibition of BMS.Methods: In this study, data set GSE43837 was screened from gene expression omnibus database, and then R language tool was used for differential analysis of its expression spectrum, The gene ontology functional enrichment and Kyoto encyclopedia of genes and genomes signal pathway enrichment analyses, as well as the interactive gene retrieval tool for hub-gene analysis, were performed.Results: According to the findings, the primary genes linked to breast cancer brain metastases are those that involve interactions between cytokines and their respective receptors and between neuroactive ligands and their respective receptors. The majority of the gene ontology enrichment took place in the extracellular structural tissues, the extracellular matrix tissues, and the second message-mediated signaling. We were able to identify 8 genes that are linked to breast cancer spreading to the brain. The gene score for matrix metallopeptidase1 (MMP-1) was the highest among them, and the genes MMP10, tumor necrosis factor alphainducible protein 8, collagen type I alpha 2 chain, vascular cell adhesion molecule 1, and TNF superfamily member 11 were all connected to 1 another in an interaction way.Conclusions: There is a possibility that the 8 key genes that were identified in this research are connected to the progression of BMS in breast cancer. Among them, MMP1 is 1 that has the potential to have a role in the diagnosis and treatment of BMS in breast cancer.Abbreviations: BBB = blood-brain barrier, BMS = brain metastasis, CC = cellular component, COL1A2 = collagen type I alpha 2 chain, GEO = gene expression omnibus, GO = gene ontology, KEGG = Kyoto encyclopedia of genes and genomes, MMP = matrix metallopeptidase, PPI = protein-protein interaction, PLCG2 = phospholipase C gamma 2, STRING = interactive gene retrieval tool, VCAM1 = vascular cell adhesion molecule 1.

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SSX2IP promotes cell proliferation and migration in breast cancer by regulating FANCI

Liu,

Zhang,

Chen

et al. 2024

Cell Biology International

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Synovial sarcoma X breakpoint 2 interacting protein (SSX2IP) is expressed in various normal tissues and participates in the progression of human cancers. Nevertheless, the specific functions and underlying molecular mechanisms of SSX2IP in cancer, particularly in breast cancer, remain poorly understood. In this study, we aimed to explore the functional role of SSX2IP in breast cancer. Immunohistochemical staining, quantitative real‐time PCR, and western blotting blot analysis were used to assess genes expression levels. By manipulating SSX2IP expression levels and conducting functional assays including Celigo cell counting assay or CCKCCK‐8‐8 assay, flow cytometry, wound healing assay, and Transwell assay, we explored the impact of SSX2IP on the malignant phenotype of breast cancer cells. Additionally, the in vivo tumor‐suppressive ability of SSX2IP was investigated by tumor xenograft experiment. Our results revealed an upregulation of SSX2IP in the breast cancer. Functional assays demonstrated that SSX2IP knockdown inhibited cell proliferation and migration, induced apoptosis in vitro, as well as suppressed the tumor growth in vivo. Conversely, SSX2IP overexpression contributed to the malignant phenotype of breast cancer cells. Co‐expression analysis showed that FA Complementation Group I (FANCI) was co‐expressed with SSX2IP. Additionally, SSX2IP positively regulated FANCI expression and its interaction was verified by Co‐IP.Co‐IP. Furthermore, FANCI overexpression partially reversed the effects of SSX2IP knockdown on cell proliferation and metastasis. In summary, our findings revealed that SSX2IP contributes to the progression of breast cancer by regulating FANCI, hinting at its potential as a novel biomarker and therapeutic target for the treatment of breast cancer.

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Network-Based Approach to Identify the Antiproliferative Mechanisms of Bruceine D in Breast Cancer From the Cancer Genome Atlas

Cited by 6 publications

References 39 publications

Bruceine D and Narclasine inhibit the proliferation of breast cancer cells and the prediction of potential drug targets

Bruceine D and Narclasine inhibit the proliferation of breast cancer cells and the prediction of potential drug targets

Screening and identification of hub-gene associated with brain metastasis in breast cancer

SSX2IP promotes cell proliferation and migration in breast cancer by regulating FANCI

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