Inhibiting of TACC3 Promotes Cell Proliferation, Cell Invasion and the EMT Pathway in Breast Cancer

Huo, Qin; Chen, Siqi; Li, Zhenwei; Wang, Juan; Xie, Ni

doi:10.3389/fgene.2021.640078

Cited by 4 publications

(3 citation statements)

References 39 publications

(58 reference statements)

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“…The Nottingham prognostic index (NPI) grade showed a consistent trend (NPI1 < NPI2 < NPI3, p < 0.0001, Figure 3i). These clinical features were all consistent with the TACC3, a tumor-related gene of breast cancer [34], which indicates that KMO could serve as a potential diagnostic indicator in breast cancer as well.…”

Section: Kmo Is Overexpressed In Patients With Aggressively Malignant Breast Cancerssupporting

confidence: 72%

Integrated Molecular Characterization to Reveal the Association between Kynurenine 3-Monooxygenase Expression and Tumorigenesis in Human Breast Cancers

Tsang

Liao

et al. 2021

JPM

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Kynurenine 3-monooxygenase (KMO) is overexpressed in several tumors and participates in the progression of breast cancer tumorigenesis, including cancer types such as triple-negative breast cancer (TNBC). This malignant gene is an enzyme in the kynurenine pathway, which is involved in the carcinogenesis of cancer through immune function manipulation. However, it remains unclear whether the role of the KMO contributes to tumorigenesis and immune functions in human breast cancer. In this study, we found that KMO was highly expressed in different types of tumors, especially in invasive ductal breast carcinoma. In addition, KMO expression was positively correlated with the malignant clinical features of patients with breast cancer, such as TNBC and a nodal-positive status, along with patients with a higher Nottingham prognostic index (NPI). Furthermore, the top ten KMO-correlated genes were the chemokines and pro-inflammatory cytokines known to be involved in the progression of various cancers, therefore, KMO may facilitate breast cancers via synergistically regulating inflammatory responses in tumors with these hub genes. Taken together, these findings highlight the tumor-promotion role of KMO in breast cancers and suggest that KMO can serve as a biomarker for prognosis prediction in breast cancer patients.

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Section: Kmo Is Overexpressed In Patients With Aggressively Malignant Breast Cancerssupporting

confidence: 72%

Integrated Molecular Characterization to Reveal the Association between Kynurenine 3-Monooxygenase Expression and Tumorigenesis in Human Breast Cancers

Tsang

Liao

et al. 2021

JPM

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“…The BP term mitotic spindle organization (involved in KG: BUB1B , AURKB, BIRC5, and TOP2A) was reported to be responsible for TNBC ( Chimplee et al, 2022 ). Integrated bioinformatics analysis reported that microtubule cytoskeleton organization involved in mitosis (involved in KG: BUB1B , AURKB, and BIRC5) and kinase binding (involved in KG: AURKB, ACTB, EGFR, and TOP2A) are significant functional term for TNBC progression ( Ryall et al, 2015 ; Huo et al, 2021 ). Therapeutic targets for TNBC treatment may interfere with the progression of TNBC by participating in the estrogen signaling pathway (involved in KG: EGFR, TOP2A, and BIRC5) ( Huang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Gene expression profile analysis to discover molecular signatures for early diagnosis and therapies of triple-negative breast cancer

Alam

Sultana

Wang

et al. 2022

Front. Mol. Biosci.

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Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer (BC), and it accounts for approximately 10%–20% of all invasive BCs diagnosed worldwide. The survival rate of TNBC in stages III and IV is very low, and a large number of patients are diagnosed in these stages. Therefore, the purpose of this study was to identify TNBC-causing molecular signatures and anti-TNBC drug agents for early diagnosis and therapies. Five microarray datasets that contained 304 TNBC and 109 control samples were collected from the Gene Expression Omnibus (GEO) database, and RNA-Seq data with 116 tumor and 124 normal samples were collected from TCGA database to identify differentially expressed genes (DEGs) between TNBC and control samples. A total of 64 DEGs were identified, of which 29 were upregulated and 35 were downregulated, by using the statistical limma R-package. Among them, seven key genes (KGs) were commonly selected from microarray and RNA-Seq data based on the high degree of connectivity through PPI (protein–protein interaction) and module analysis. Out of these seven KGs, six KGs (TOP2A, BIRC5, AURKB, ACTB, ASPM, and BUB1B) were upregulated and one (EGFR) was downregulated. We also investigated their differential expression patterns with different subtypes and progression stages of BC by the independent datasets of RNA-seq profiles from UALCAN database, which indicated that they may be potential biomarkers for early diagnosis. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses with the proposed DEGs were performed using the online Enrichr database to investigate the pathogenetic processes of TNBC highlighting KGs. Then, we performed gene regulatory network analysis and identified three transcriptional (SOX2, E2F4, and KDM5B) and three post-transcriptional (hsa-mir-1-3p, hsa-mir-124-3p, and hsa-mir-34a-5p) regulators of KGs. Finally, we proposed five KG-guided repurposable drug molecules (imatinib, regorafenib, pazopanib, teniposide, and dexrazoxane) for TNBC through network pharmacology and molecular docking analyses. These drug molecules also showed significant binding performance with some cancer-related PTM-sites (phosphorylation, succinylation, and ubiquitination) of top-ranked four key proteins (EGFR, AURKB, BIRC5, and TOP2A). Therefore, the findings of this computational study may play a vital role in early diagnosis and therapies against TNBC by wet-lab validation.

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“…Despite advances in research and treatment methods, the incidence of breast cancer continues to rise. 3,4 As a result, finding new prognostic and diagnostic biomarkers for breast cancer is critical.…”

Section: Introductionmentioning

confidence: 99%

Identification of GZMA as a Potential Therapeutic Target Involved in Immune Infiltration in Breast Cancer by Integrated Bioinformatical Analysis

Huo¹,

Ning²,

Xie³

2023

BCTT

Self Cite

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Purpose: Granzyme A (GZMA) is a potential prognostic target for various cancer types. However, its therapeutic significance in breast cancer with immune infiltration remains controversial. We analyzed GZMA expression and its prognostic value in breast cancer with immune cell infiltration. Patients and methods: Data was obtained from patients with breast cancer registered at The Cancer Genome Atlas. A correlation was performed between GZMA expression and patient's clinicopathological features such as age, pathologic stage, metastasis stage, overall survival (OS), disease-specific survival (DSS), and progress free interval (PFI). Kaplan-Meier analyses and Cox proportional hazard regression model were used to examine the predictive significance of GZMA expression for breast cancer. The co-expression pattern of GZMA was assessed by the LinkedOmics web portal. The relationship between GZMA expression and immune cells was analyzed using the TIMER database. The correlation between GZMA and lymphocytes and immunomodulators was established with the TISIDB database. Results: There was a lower GZMA expression in breast cancer tissue than in normal tissue. Interestingly, GZMA expression was associated with age, pathologic stage, and the Tumour, Node, and Metastasis stage. Overexpression of GZMA was also associated with better OS, DSS, and PFI. Based on the Cox regression analysis, GZMA was identified as an independent favorable prognostic factor for breast cancer. Our findings demonstrated a strong association between GZMA and T-cell checkpoints (PD-1, PD-L1, and cytotoxic T lymphocyte-associated antigen (CTLA-4)) in breast cancer. Moreover, we evaluated the interactions between GZMA expression and markers of dendritic and CD8+ T cells using quantitative immunofluorescence. We discovered that increased infiltration of dendritic and CD8+ T cells was associated with GZMA expression in breast cancer. Conclusion: GZMA expression is associated with a favorable prognosis in breast cancer and is significantly correlated with immune cell infiltration. GZMA may be considered a promising therapeutic target for patients with breast cancer.

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Inhibiting of TACC3 Promotes Cell Proliferation, Cell Invasion and the EMT Pathway in Breast Cancer

Cited by 4 publications

References 39 publications

Integrated Molecular Characterization to Reveal the Association between Kynurenine 3-Monooxygenase Expression and Tumorigenesis in Human Breast Cancers

Integrated Molecular Characterization to Reveal the Association between Kynurenine 3-Monooxygenase Expression and Tumorigenesis in Human Breast Cancers

Gene expression profile analysis to discover molecular signatures for early diagnosis and therapies of triple-negative breast cancer

Identification of GZMA as a Potential Therapeutic Target Involved in Immune Infiltration in Breast Cancer by Integrated Bioinformatical Analysis

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