scholarly journals Histone 3 Lysine 27 Trimethylation Signature in Breast Cancer

2021 ◽  
Vol 22 (23) ◽  
pp. 12853
Author(s):  
Lidia Borkiewicz
Keyword(s):  
Breast Cancer ◽  
Cancer Biology ◽  
Complex Disease ◽  
Chromatin Modification ◽  
Tumour Suppressor Genes ◽  
Gene Promoters ◽  
Cancer Subtypes ◽  
H3k27 Methylation ◽  
Histone 3 ◽  
Tumorigenesis And Progression

Cancer development and progression rely on complicated genetic and also epigenetic changes which regulate gene expression without altering the DNA sequence. Epigenetic mechanisms such as DNA methylation, histone modifications, and regulation by lncRNAs alter protein expression by either promoting gene transcription or repressing it. The presence of so-called chromatin modification marks at various gene promoters and gene bodies is associated with normal cell development but also with tumorigenesis and progression of different types of cancer, including the most frequently diagnosed breast cancer. This review is focused on the significance of one of the abundant post-translational modifications of histone 3- trimethylation of lysine 27 (H3K27me3), which was shown to participate in tumour suppressor genes’ silencing. Unlike other reviews in the field, here the overview of existing evidence linking H3K27me3 status with breast cancer biology and the tumour outcome is presented especially in the context of diverse breast cancer subtypes. Moreover, the potential of agents that target H3K27me3 for the treatment of this complex disease as well as H3K27 methylation in cross-talk with other chromatin modifications and lncRNAs are discussed.

scholarly journals Information theoretic sub-network mining characterizes breast cancer subtypes in terms of cancer core mechanisms

2016 ◽  
Vol 14 (05) ◽  
pp. 1644002 ◽  
Author(s):  
Jinwoo Park ◽  
Benjamin Hur ◽  
Sungmin Rhee ◽  
Sangsoo Lim ◽  
Min-Su Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regulatory Network ◽  
Cancer Biology ◽  
Breast Cancer Subtype ◽  
Breast Cancer Subtypes ◽  
Information Theoretic ◽  
Cancer Subtypes ◽  
Network Mining ◽  
Subtype Classification ◽  
Cancer Subtype

A breast cancer subtype classification scheme, PAM50, based on genetic information is widely accepted for clinical applications. On the other hands, experimental cancer biology studies have been successful in revealing the mechanisms of breast cancer and now the hallmarks of cancer have been determined to explain the core mechanisms of tumorigenesis. Thus, it is important to understand how the breast cancer subtypes are related to the cancer core mechanisms, but multiple studies are yet to address the hallmarks of breast cancer subtypes. Therefore, a new approach that can explain the differences among breast cancer subtypes in terms of cancer hallmarks is needed. We developed an information theoretic sub-network mining algorithm, differentially expressed sub-network and pathway analysis (DeSPA), that retrieves tumor-related genes by mining a gene regulatory network (GRN) of transcription factors and miRNAs. With extensive experiments of the cancer genome atlas (TCGA) breast cancer sequencing data, we showed that our approach was able to select genes that belong to cancer core pathways such as DNA replication, cell cycle, p53 pathways while keeping the accuracy of breast cancer subtype classification comparable to that of PAM50. In addition, our method produces a regulatory network of TF, miRNA, and their target genes that distinguish breast cancer subtypes, which is confirmed by experimental studies in the literature.

scholarly journals Deconvolution of DNA methylation signatures identifies common differentially methylated gene regions on 1p36 across breast cancer subtypes

2017 ◽  
Author(s):  
Alexander J. Titus ◽  
Gregory P. Way ◽  
Kevin C. Johnson ◽  
Brock C. Christensen
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Complex Disease ◽  
Molecular Subtype ◽  
Early Stage ◽  
The Cancer Genome Atlas ◽  
Data Set ◽  
Disease Heterogeneity ◽  
Cancer Subtypes ◽  
Differentially Methylated Gene

ABSTRACTBreast cancer is a complex disease and studying DNA methylation (DNAm) in tumors is complicated by disease heterogeneity. We compared DNAm in breast tumors with normal-adjacent breast samples from The Cancer Genome Atlas (TCGA). We constructed models stratified by tumor stage and PAM50 molecular subtype and performed cell-type reference-free deconvolution on each model. We identified nineteen differentially methylated gene regions (DMGRs) in early stage tumors across eleven genes (AGRN, C1orf170, FAM41C, FLJ39609, HES4, ISG15, KLHL17, NOC2L, PLEKHN1, SAMD11, WASH5P). These regions were consistently differentially methylated in every subtype and all implicated genes are localized on chromosome 1p36.3. We also validated seventeen DMGRs in an independent data set. Identification and validation of shared DNAm alterations across tumor subtypes in early stage tumors advances our understanding of common biology underlying breast carcinogenesis and may contribute to biomarker development. We also provide evidence on the importance and potential function of 1p36 in cancer.

scholarly journals Expression patterns of LncRNA-GAS5 and its target APOBEC3C gene through miR-103 in breast cancer patients

2021 ◽  
Vol 67 (3) ◽  
pp. 5-10
Author(s):  
Belan O. Kanabe ◽  
Mehmet Ozaslan ◽  
Sherwan Ahmed Aziz ◽  
Mustafa S. Al-Attar ◽  
İbrahim Halil Kılıç ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Biology ◽  
Expression Patterns ◽  
Immunohistochemical Analysis ◽  
Expression Level ◽  
Breast Cancer Patients ◽  
Cancer Subtypes ◽  
Lncrna Gas5

Early diagnosis of breast cancer can increase the survivability of the patients and the patient’s quality of life. There is growing evidence demonstrating the active role of LncRNA-GAS5 and miR-103 in cancer biology. APOBEC enzymes are important players in immunity and may contribute to carcinogenesis. Mutation and expression alteration in the APOBEC gene family was found to have a strong correlation with breast cancer risk. This study aimed to evaluate the expression level of lncRNA-GAS5 and its target APOBEC3C in women with breast cancer through expression evaluation of miR-103. Moreover, the interaction between lncRNA-GAS5 and miR-103 was studied. In the present study, forty paired tumor and normal samples classified based on breast cancer subtypes and clinical features of patients were analyzed using gene expression studies. Immunohistochemical analysis of the gene products was performed to classify tumors. The RNA samples were extracted from breast tissue. Real-time PCR was conducted for APOBEC3C and Lnc-RNA GAS5 expression. In addition, miR-103a miScript Primer Assay was utilized for the expression of miR-103-5p. It was revealed that the expression level of APOBEC3C and lncRNA-GAS5 were significantly down-regulated; however, the miRNA-103 expression level was significantly up-regulated. GAS5 expression was positively correlated with APOBEC3C expression and negatively correlated with miR-103 expression. In conclusion, we observed down-regulation of APOBEC3C and LncRNA-GAS5 and up-regulation of miRNA 103 in breast cancer patients. The expression of GAS5 may provide a new potential treatment target for breast cancer. To clarify the role of these molecules in the cellular signaling pathways, further studies are required.

scholarly journals EP300 and SIRT1/6 Co-Regulate Lapatinib Sensitivity Via Modulating FOXO3-Acetylation and Activity in Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1067 ◽  
Author(s):  
Zimam Mahmud ◽  
Ana R. Gomes ◽  
Hee Jin Lee ◽  
Sathid Aimjongjun ◽  
Yannasittha Jiramongkol ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Target Gene ◽  
Target Genes ◽  
Ectopic Expression ◽  
Sirtuin 1 ◽  
Fine Tuning ◽  
Gene Promoters ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Cancer Subtypes

Forkhead Box O3 (FOXO3) is a tumor suppressor whose activity is fine-tuned by post-translational modifications (PTMs). In this study, using the BT474 breast cancer cells and a recently established lapatinib resistant (BT474-LapR) cell line, we observed that higher FOXO3 and acetylated (Ac)-FOXO3 levels correlate with lapatinib sensitivity. Subsequent ectopic expression of EP300 led to an increase in acetylated-FOXO3 in sensitive but not in resistant cells. Drug sensitivity assays revealed that sensitive BT474 cells show increased lapatinib cytotoxicity upon over-expression of wild-type but not acetylation-deficient EP300. Moreover, FOXO3 recruitment to target gene promoters is associated with target gene expression and drug response in sensitive cells and the inability of FOXO3 to bind its target genes correlates with lapatinib-resistance in BT474-LapR cells. In addition, using SIRT1/6 specific siRNAs and chemical inhibitor, we also found that sirtuin 1 and -6 (SIRT1 and -6) play a part in fine-tuning FOXO3 acetylation and lapatinib sensitivity. Consistent with this, immunohistochemistry results from different breast cancer subtypes showed that high SIRT6/1 levels are associated with constitutive high FOXO3 expression which is related to FOXO3 deregulation/inactivation and poor prognosis in breast cancer patient samples. Collectively, our results suggest the involvement of FOXO3 acetylation in regulating lapatinib sensitivity of HER2-positive breast cancers.

Identification of new therapeutic leads for triple negative breast cancer subtypes

Planta Medica ◽  
2015 ◽  
Vol 81 (11) ◽  
Author(s):  
AJ Robles ◽  
L Du ◽  
S Cai ◽  
RH Cichewicz ◽  
SL Mooberry
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Subtypes ◽  
Cancer Subtypes ◽  
Therapeutic Leads

The Impact of Translational Research in Breast Cancer Care: Can we Improve the Therapeutic Scenario?

2018 ◽  
Vol 18 (6) ◽  
pp. 832-836
Author(s):  
Giuseppe Buono ◽  
Francesco Schettini ◽  
Francesco Perri ◽  
Grazia Arpino ◽  
Roberto Bianco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Translational Research ◽  
Cell Biology ◽  
Cancer Biology ◽  
Hormone Receptors ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Molecular Heterogeneity ◽  
Therapeutic Implications ◽  
The Impact

Traditionally, breast cancer (BC) is divided into different subtypes defined by immunohistochemistry (IHC) according to the expression of hormone receptors and overexpression/amplification of human epidermal growth factor receptor 2 (HER2), with crucial therapeutic implications. In the last few years, the definition of different BC molecular subgroups within the IHC-defined subtypes and the identification of the important role that molecular heterogeneity can play in tumor progression and treatment resistance have inspired the search for personalized therapeutic approaches. In this scenario, translational research represents a key strategy to apply knowledge from cancer biology to the clinical setting, through the study of all the tumors “omics”, including genomics, transcriptomics, proteomics, epigenomics, and metabolomics. Importantly, the introduction of new high-throughput technologies, such as next generation sequencing (NGS) for the study of cancer genome and transcriptome, greatly amplifies the potential and the applications of translational research in the oncology field. Moreover, the introduction of new experimental approaches, such as liquid biopsy, as well as new-concept clinical trials, such as biomarker-driven adaptive studies, may represent a turning point for BC translational research. </P><P> It is likely that translational research will have in the near future a significant impact on BC care, especially by giving us the possibility to dissect the complexity of tumor cell biology and develop new personalized treatment strategies.

scholarly journals DNA Methylation Based Molecular Subtypes Predict Prognosis in Breast Cancer Patients

2021 ◽  
Vol 28 ◽  
pp. 107327482098851
Author(s):  
Zeng-Hong Wu ◽  
Yun Tang ◽  
Yan Zhou
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Molecular Subtypes ◽  
Methylation Status ◽  
The Cancer Genome Atlas ◽  
Training Dataset ◽  
Consensus Clustering ◽  
Breast Cancer Patients ◽  
Cancer Subtypes ◽  
Novel Biomarkers

Background: Epigenetic changes are tightly linked to tumorigenesis development and malignant transformation’ However, DNA methylation occurs earlier and is constant during tumorigenesis. It plays an important role in controlling gene expression in cancer cells. Methods: In this study, we determining the prognostic value of molecular subtypes based on DNA methylation status in breast cancer samples obtained from The Cancer Genome Atlas database (TCGA). Results: Seven clusters and 204 corresponding promoter genes were identified based on consensus clustering using 166 CpG sites that significantly influenced survival outcomes. The overall survival (OS) analysis showed a significant prognostic difference among the 7 groups (p<0.05). Finally, a prognostic model was used to estimate the results of patients on the testing set based on the classification findings of a training dataset DNA methylation subgroups. Conclusions: The model was found to be important in the identification of novel biomarkers and could be of help to patients with different breast cancer subtypes when predicting prognosis, clinical diagnosis and management.

scholarly journals Collagen molecular phenotypic switch between non-neoplastic and neoplastic canine mammary tissues

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masahiko Terajima ◽  
Yuki Taga ◽  
Becky K. Brisson ◽  
Amy C. Durham ◽  
Kotaro Sato ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Mammary Carcinoma ◽  
Cancer Biology ◽  
Type I Collagen ◽  
Critical Role ◽  
Premature Death ◽  
Mammary Tissue ◽  
Type I ◽  
Cross Links

AbstractIn spite of major advances over the past several decades in diagnosis and treatment, breast cancer remains a global cause of morbidity and premature death for both human and veterinary patients. Due to multiple shared clinicopathological features, dogs provide an excellent model of human breast cancer, thus, a comparative oncology approach may advance our understanding of breast cancer biology and improve patient outcomes. Despite an increasing awareness of the critical role of fibrillar collagens in breast cancer biology, tumor-permissive collagen features are still ill-defined. Here, we characterize the molecular and morphological phenotypes of type I collagen in canine mammary gland tumors. Canine mammary carcinoma samples contained longer collagen fibers as well as a greater population of wider fibers compared to non-neoplastic and adenoma samples. Furthermore, the total number of collagen cross-links enriched in the stable hydroxylysine-aldehyde derived cross-links was significantly increased in neoplastic mammary gland samples compared to non-neoplastic mammary gland tissue. The mass spectrometric analyses of type I collagen revealed that in malignant mammary tumor samples, lysine residues, in particular those in the telopeptides, were markedly over-hydroxylated in comparison to non-neoplastic mammary tissue. The extent of glycosylation of hydroxylysine residues was comparable among the groups. Consistent with these data, expression levels of genes encoding lysyl hydroxylase 2 (LH2) and its molecular chaperone FK506-binding protein 65 were both significantly increased in neoplastic samples. These alterations likely lead to an increase in the LH2-mediated stable collagen cross-links in mammary carcinoma that may promote tumor cell metastasis in these patients.

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