Disabled‐1 is down‐regulated in clinical breast cancer and regulates cell apoptosis through <scp>NF</scp>‐κB/Bcl‐2/caspase‐9

Cao, Ruihua; Li, Kai; Xing, Wen; Du, Shuyuan; Li, Qiang; Zhu, Xuemei; Cui, Shusen

doi:10.1111/jcmm.14047

Cited by 12 publications

(7 citation statements)

References 17 publications

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“…Somatic mutation of GATA3 is associated with clinicopathological features and expression of TCGA in breast cancer patients (30). FANCD2 (31), DAB1 (32) and ANK3 (33) are all supported by literature to be associated with breast cancer.…”

Section: Tmb Analysismentioning

confidence: 85%

HAUS5 Is A Potential Prognostic Biomarker With Functional Significance in Breast Cancer

et al. 2022

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BackgroundBreast cancer (BRCA) has become the most frequently appearing, lethal, and aggressive cancer with increasing morbidity and mortality. Previously, it was discovered that the HAUS5 protein is involved in centrosome integrity, spindle assembly, and the completion of the cytoplasmic division process during mitosis. By encouraging chromosome misdivision and aneuploidy, HAUS5 has the potential to cause cancer. The significance of HAUS5 in BRCA and the relationship between its expression and clinical outcomes or immune infiltration remains unclear.MethodsPan-cancer was analyzed by TIMER2 web and the expression differential of HAUS5 was discovered. The prognostic value of HAUS5 for BRCA was evaluated with KM plotter and confirmed with Gene Expression Omnibus (GEO) dataset. Following that, we looked at the relationship between the high and low expression groups of HAUS5 and breast cancer clinical indications. Signaling pathways linked to HAUS5 expression were discovered using Gene Set Enrichment Analysis (GSEA). The relative immune cell infiltrations of each sample were assessed using the CIBERSORT algorithm and ESTIMATE method. We evaluated the Tumor Mutation Burden (TMB) value between the two sets of samples with high and low HAUS5 expression, as well as the differences in gene mutations between the two groups. The proliferation changes of BRCA cells after knockdown of HAUS5 were evaluated by fluorescence cell counting and colony formation assay.ResultHAUS5 is strongly expressed in most malignancies, and distinct associations exist between HAUS5 and prognosis in BRCA patients. Upregulated HAUS5 was associated with poor clinicopathological characteristics such as tumor T stage, ER, PR, and HER2 status. mitotic prometaphase, primary immunodeficiency, DNA replication, cell cycle related signaling pathways were all enriched in the presence of elevated HAUS5 expression, according to GSEA analysis. The BRCA microenvironment’s core gene, HAUS5, was shown to be related with invading immune cell subtypes and tumor cell stemness. TMB in the HAUS5-low expression group was significantly higher than that in the high expression group. The mutation frequency of 15 genes was substantially different in the high expression group compared to the low expression group. BRCA cells’ capacity to proliferate was decreased when HAUS5 was knocked down.ConclusionThese findings show that HAUS5 is a positive regulator of BRCA progression that contributes to BRCA cells proliferation. As a result, HAUS5 might be a novel prognostic indicator and therapeutic target for BRCA patients.

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Section: Tmb Analysismentioning

confidence: 85%

HAUS5 Is A Potential Prognostic Biomarker With Functional Significance in Breast Cancer

et al. 2022

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“…The results of Zhou et al (2019) (29) showed that the PR of Bcl-2 in MGT was 28.42%, and there was no statistically obvious difference from the control normal MGT, which was contrary to the results of this study. The possible reason was that Bcl-2 had both anti-proliferation and anti-apoptosis effects in cells, and was expressed in normal MGT, which could regulate the normal tissue to survive rather than apoptosis (30). Studies showed that with the cell proliferation, the anti-proliferation effect of Bcl-2 gradually weakened, showing the anti-apoptotic activity, so the expression level of Bcl-2 in the early stage of the tumor was not greatly changed.…”

Section: Analysis Of Bc Cell Apoptosis Detection Resultsmentioning

confidence: 99%

Effects of 7,12-Dimethylbenz(a)anthracene on Apoptosis of Breast Cancer Cells through Regulating Expressions of FasL and Bcl-2

Lin

Guan

Zhou

et al. 2022

Cell Mol Biol (Noisy-le-grand)

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To provides a reference basis for the apoptosis of breast cancer (BC) cells and the carcinogenesis of BC, the effects of 7, 12-dimethylbenz (a) anthracene (DMBA) on apoptosis regulators FasL and B-cell lymphoma-2 (Bcl-2) were investigated. In this study, 62 female C57BL/6 mice aged from 4 to 6 weeks were randomly divided into control group (CG) and test group (TG), with 31 mice in each group. The TG was given DMBA solution by gavage at a dose of 50 mg/kg, and the CG was given normal saline of equal volume. On the second day after the experiment, all the mice were killed by cervical dislocation. The morphology of the mammary gland was observed by hematoxylin-eosin (HE) staining, and the differences of FasL and Bcl-2 protein expression (PE) were detected by immunohistochemistry. The mRNA expression levels of FasL and Bcl-2 were detected by quantitative real-time PCR (qPCR). Breast cell apoptosis status of mice in the two groups was detected by the terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labelling (TUNEL) method. The results showed that after HE staining, the tumor cells in the TG were stacked up to form a substantial structure. The expression level of FasL protein in the CG was greatly lower than that in the TG, and the positive rate (PR) was 20.25%, which was greatly lower than that of 89.65% in the TG (P<0.01). The expression level of Bcl-2 protein in the mammary gland tissues (MGTs) of mice in the TG was greatly higher than that of the CG, and its PR was 87.96%, which was greatly higher than that of 31.48% in the CG (P<0.01). The expression levels of FasL mRNA in the MGTs of mice in the TG and CG were 5.82±4.37 and 1.27±0.12, respectively, and there was a statistically obvious difference (P<0.05). The mRNA expression levels of Bcl-2 in the TG and the CG were 18.97±2.65 and 2.02±0.54, respectively, and there was an extremely obvious difference (P<0.01). The apoptosis rate of mammary gland cells in the TG was (19.79±3.53) %, and that in the CG was (2.93±0.28) %, and there was an extremely obvious difference (P<0.01). It indicated that DMBA inhibited the apoptosis of BC cells by regulating the up-regulation of FasL and Bcl-2 expression.

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“…The upregulation of DAB1 mediated the inhibition of migration and invasion of prostate cancer cells by regulating microRNA-300 [56]. Dab1 promoted cell apoptosis by regulating NF-κB/Bcl-2/caspase-9 pathway, considered as a potential tumor suppressor gene of breast cancer [57]. indicating the necessary to develop the method for dissecting the personalized driver mechanism for GBM individuals.…”

Section: Discussionmentioning

confidence: 99%

“…The upregulation of DAB1 mediated the inhibition of migration and invasion of prostate cancer cells by regulating microRNA‐300 [ 56 ]. Dab1 promoted cell apoptosis by regulating NF‐κB/Bcl‐2/caspase‐9 pathway, considered as a potential tumor suppressor gene of breast cancer [ 57 ]. In vivo , DAB ‐1 could inhibit tumor growth, metastasis formation, and mortality rate of ectopic and orthotopic tumors [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Identifying the personalized driver gene sets maximally contributing to abnormality of transcriptome phenotype in glioblastoma multiforme individuals

Pang

Lan

et al. 2023

Molecular Oncology

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High heterogeneity in genome and phenotype of cancer populations made it difficult to apply population‐based common driver genes to the diagnosis and treatment of cancer individuals. Characterizing and identifying the personalized driver mechanism for glioblastoma multiforme (GBM) individuals were pivotal for the realization of precision medicine. We proposed an integrative method to identify the personalized driver gene sets by integrating the profiles of gene expression and genetic alterations in cancer individuals. This method coupled genetic algorithm and random walk to identify the optimal gene sets that could explain abnormality of transcriptome phenotype to the maximum extent. The personalized driver gene sets were identified for 99 GBM individuals using our method. We found that genomic alterations in between one and seven driver genes could maximally and cumulatively explain the dysfunction of cancer hallmarks across GBM individuals. The driver gene sets were distinct even in GBM individuals with significantly similar transcriptomic phenotypes. Our method identified MCM4 with rare genetic alterations as previously unknown oncogenic genes, the high expression of which were significantly associated with poor GBM prognosis. The functional experiments confirmed that knockdown of MCM4 could significantly inhibit proliferation, invasion, migration, and clone formation of the GBM cell lines U251 and U118MG, and overexpression of MCM4 significantly promoted the proliferation, invasion, migration, and clone formation of the GBM cell line U87MG. Our method could dissect the personalized driver genetic alteration sets that are pivotal for developing targeted therapy strategies and precision medicine. Our method could be extended to identify key drivers from other levels and could be applied to more cancer types.

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Disabled‐1 is down‐regulated in clinical breast cancer and regulates cell apoptosis through NF‐κB/Bcl‐2/caspase‐9

Cited by 12 publications

References 17 publications

HAUS5 Is A Potential Prognostic Biomarker With Functional Significance in Breast Cancer

HAUS5 Is A Potential Prognostic Biomarker With Functional Significance in Breast Cancer

Effects of 7,12-Dimethylbenz(a)anthracene on Apoptosis of Breast Cancer Cells through Regulating Expressions of FasL and Bcl-2

Identifying the personalized driver gene sets maximally contributing to abnormality of transcriptome phenotype in glioblastoma multiforme individuals

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