Abstract 3608: Identification of differentially expressed genes in 4T1 mice triple-negative mammary gland cancer during the early phase of combination treatment with indomethacin and radiation

2020 ◽  
Author(s):  
Robert Yuk Sing Cheng ◽  
Lisa Ridnour ◽  
Timothy Back ◽  
Debashree Basudhar ◽  
Stephen Anderson ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Differentially Expressed Genes ◽  
Combination Treatment ◽  
Early Phase ◽  
Triple Negative ◽  
Differentially Expressed ◽  
Mammary Gland Cancer

scholarly journals Regulatory Crosstalk of Doxorubicin, Estradiol and TNFα Combined Treatment in Breast Cancer-derived Cell Lines

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Isar Nassiri ◽  
Alberto Inga ◽  
Erna Marija Meškytė ◽  
Federica Alessandrini ◽  
Yari Ciribilli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Differentially Expressed Genes ◽  
Combination Treatment ◽  
Combined Treatment ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Transcriptional Responses ◽  
Predisposing Factor ◽  
Inflammatory Microenvironment

Abstract We present a new model of ESR1 network regulation based on analysis of Doxorubicin, Estradiol, and TNFα combination treatment in MCF-7. We used Doxorubicin as a therapeutic agent, TNFα as marker and mediator of an inflammatory microenvironment and 17β-Estradiol (E2) as an agonist of Estrogen Receptors, known predisposing factor for hormone-driven breast cancer, whose pharmacological inhibition reduces the risk of breast cancer recurrence. Based on the results of transcriptomics analysis, we found 71 differentially expressed genes that are specific for the combination treatment with Doxorubicin + Estradiol + TNFα in comparison with single or double treatments. The responsiveness to the triple treatment was examined for seven genes by qPCR, of which six were validated, and then extended to four additional cell lines differing for p53 and/or ER status. The results of differential regulation enrichment analysis highlight the role of the ESR1 network that included 36 of 71 specific differentially expressed genes. We propose that the combined activation of p53 and NF-kB transcription factors significantly influences ligand-dependent, ER-driven transcriptional responses, also of the ESR1 gene itself. These results provide a model of coordinated interaction of TFs to explain the Doxorubicin, E2 and TNFα induced repression mechanisms.

scholarly journals Identification of miRNAs and differentially expressed genes in early phase non-small cell lung cancer

2016 ◽  
Vol 35 (4) ◽  
pp. 2171-2176 ◽  
Author(s):  
WEN TIAN ◽  
JIE LIU ◽  
BAOJING PEI ◽  
XIAOBO WANG ◽  
YU GUO ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Differentially Expressed Genes ◽  
Cell Lung Cancer ◽  
Early Phase ◽  
Small Cell ◽  
Differentially Expressed ◽  
Small Cell Lung

scholarly journals Identification of regulatory networks and hub genes controlling mammary gland development and lactation in dairy goats during the late lactation, dry period, and late gestation stages

2020 ◽  
Author(s):  
Rong Xuan ◽  
Tianle Chao ◽  
Xiaodong Zhao ◽  
Aili Wang ◽  
Yunpeng Chu ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Mammary Gland ◽  
Differentially Expressed Genes ◽  
Mammary Gland Development ◽  
Late Gestation ◽  
Differentially Expressed ◽  
Dry Period ◽  
Mammary Gland Tissue ◽  
Three Stages ◽  
Gland Development

Abstract Background From the late lactation to late gestation stages, the mammary gland tissue of goats undergoes a process from involution to remodeling and then to high differentiation of mammary gland tissue. From the perspective of lactation, this is a continuous development process of the goat mammary gland from the termination of lactation to the restoration of lactation. We performed transcriptome sequencing on goat mammary gland tissues at three mammary gland developmental stages to screen for differentially expressed genes that affect mammary gland development and the physiological process of lactation and mapped their expression profiles in three stages. The objective of this study is to reveal the expression characteristics of these genes and their potential function during mammary gland development and lactation. Results We identified 1,381 differentially expressed genes in the mammary gland during three stages and found that the expression level of genes encoding casein, such as alpha-s1-casein (CSN1S1), alpha-s2-casein (CSN1S2), beta-casein (CSN2), and kappa-casein (CSN3), and alpha-lactalbumin (LALBA) were higher in mammary gland tissues during the late lactation stage and late gestation stage than those during the dry period. In addition, we constructed six functional networks related to differentially expressed genes and found that these genes are closely related to mammary gland growth and development, apoptosis, immunity, substance transport, biosynthesis, and metabolism. Finally, we identified 35 differentially expressed transcription factors, which were classified into 16 families, and predicted that transcription factors of the basic leucine zipper domain (bZIP) family and basic helix-loop-helix (bHLH) family regulated the expression levels of genes related to mammary gland development and lactation. Conclusions Among the late lactation, dry period, and late gestation stages, there are differences in the expression levels of genes related to mammary gland growth and development, apoptosis, immunity, basic substance transport, biosynthesis, and metabolism in mammary gland tissues. Some genes in the same family or with similar functions have similar expression patterns. These differentially expressed genes or transcription factors work synergistically to participate in the regulation of mammary gland development and the physiological process of lactation.

scholarly journals Identification of Immune-Related Risk Characteristics and Prognostic Value of Immunophenotyping in TNBC

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiarong Yi ◽  
Zeyu Shuang ◽  
Wenjing Zhong ◽  
Haoming Wu ◽  
Jikun Feng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Differentially Expressed Genes ◽  
Triple Negative Breast Cancer ◽  
Evaluation System ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Evaluation Tool ◽  
Her 2

Background: Triple-negative breast cancer (TNBC) is not sensitive to targeted therapy with HER-2 monoclonal antibody and endocrine therapy due to lack of ER, PR, and HER-2 receptors. TNBC is a breast cancer subtype with the worst prognosis and the highest mortality rate compared with other subtypes.Materials and Methods: Breast cancer-related data were retrieved from The Cancer Genome Atlas (TCGA) database, and 116 cases of triple-negative breast cancer were identified from the data. GSE31519 dataset was retrieved from Gene Expression Omnibus (GEO) database, comprising a total of 68 cases with TNBC. Survival analysis was performed based on immune score, infiltration score and mutation score to explore differences in prognosis of different immune types. Analysis of differentially expressed genes was conducted and GSEA analysis based on these genes was conducted to explore the potential mechanism.Results: The findings showed that comprehensive immune typing is highly effective and accurate in assessing prognosis of TNBC patients. Analysis showed that MMP9, CXCL9, CXCL10, CXCL11 and CD7 are key genes that may affect immune typing of TNBC patients and play an important role in prediction of prognosis in TNBC patients.Conclusion: The current study presents an evaluation system based on immunophenotyping, which provides a more accurate prognostic evaluation tool for TNBC patients. Differentially expressed genes can be targeted to improve treatment of TNBC.

scholarly journals Comprehensive MicroRNA Expression Profile of the Mammary Gland in Lactating Dairy Cows With Extremely Different Milk Protein and Fat Percentages

2020 ◽  
Vol 11 ◽  
Author(s):  
Xiaogang Cui ◽  
Shengli Zhang ◽  
Qin Zhang ◽  
Xiangyu Guo ◽  
Changxin Wu ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Rna Sequencing ◽  
Differentially Expressed Genes ◽  
Small Rna ◽  
Milk Protein ◽  
Milk Composition ◽  
Differentially Expressed ◽  
Small Rna Sequencing ◽  
Rna Seq

A total of 31 differentially expressed genes in the mammary glands were identified in our previous study using RNA sequencing (RNA-Seq), for lactating cows with extremely high and low milk protein and fat percentages. To determine the regulation of milk composition traits, we herein investigated the expression profiles of microRNA (miRNA) using small RNA sequencing based on the same samples as in the previous RNA-Seq experiment. A total of 497 known miRNAs (miRBase, release 22.1) and 49 novel miRNAs among the reads were identified. Among these miRNAs, 71 were found differentially expressed between the high and low groups (p < 0.05, q < 0.05). Furthermore, 21 of the differentially expressed genes reported in our previous RNA-Seq study were predicted as target genes for some of the 71 miRNAs. Gene ontology and KEGG pathway analyses showed that these targets were enriched for functions such as metabolism of protein and fat, and development of mammary gland, which indicating the critical role of these miRNAs in regulating the formation of milk protein and fat. With dual luciferase report assay, we further validated the regulatory role of 7 differentially expressed miRNAs through interaction with the specific sequences in 3′UTR of the targets. In conclusion, the current study investigated the complexity of the mammary gland transcriptome in dairy cattle using small RNA-seq. Comprehensive analysis of differential miRNAs expression and the data from previous study RNA-seq provided the opportunity to identify the key candidate genes for milk composition traits.

scholarly journals Investigation of Candidate Genes and Pathways in Basal/TNBC Patients by Integrated Analysis

2021 ◽  
Vol 20 ◽  
pp. 153303382110195
Author(s):  
Qi Liu ◽  
Xiang Song ◽  
Zhaoyun Liu ◽  
Zhiyong Yu
Keyword(s):  
Breast Cancer ◽  
Survival Analysis ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Differentially Expressed ◽  
Breast Cancer Cell Lines ◽  
Integrated Analysis ◽  
Transcription Activator ◽  
Luminal Type

Purpose: This study aims to identify the key pathway and related genes and to further explore the potential molecular mechanisms of triple negative breast cancer (TNBC). Methods: The transcriptome data and clinical information of breast cancer patients were downloaded from the TCGA database, including 94 cases of paracancerous tissue, 225 cases of Basal like type, 151 cases of Her2 type, 318 cases of Luminal type A, 281 cases of Luminal type B, and 89 cases of Normal Like type. The differentially expressed genes (DEGs) were identified based on the criteria of |logFC|≥1.5 and adjust P < 0.001.Their functions were annotated by gene ontology (GO) analysis and Kyoto Encyclopedia of differentially expressed genes & Genomes (KEGG) pathway analysis. Cox regression univariate analysis and Kaplan-Meier survival curves (Log-rank method) were used for survival analysis. FOXD1, DLL3 and LY6D were silenced in breast cancer cell lines, and cell viability was assessed by CCK-8 assay. Further, the expression of FOXD1, DLL3 and LY6D were explored by immunohistochemistry on triple negative breast tumor tissue and normal breast tissue. Results: A total of 533 DEGs were identified. Functional annotation showed that DEGs were significantly enriched in intermediate filament cytoskeleton, DNA−binding transcription activator activity, epidermis development, and Neuroactive ligand−receptor interaction. Survival analysis found that FOXD1, DLL3, and LY6D showed significant correlation with the prognosis of patients with the Basal-like type ( P < 0.05). CCK-8 assay showed that compared with Doxorubicin alone group, the cytotoxicity of Doxorubicin combined with siRNA-knockdown of FOXD1, DLL3, or LY6D was much significant. Conclusion: The DEGs and their enriched functions and pathways identified in this study contribute to the understanding of the molecular mechanisms of TNBC. In addition, FOXD1, DLL3, and LY6D may be defined as the prognostic markers and potential therapeutic targets for TNBC patients.

scholarly journals Investigating the effect of positional variation on mid-lactation mammary gland transcriptomics in mice fed either a low-fat or high-fat diet

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255770
Author(s):  
Adrienne A. Cheng ◽  
Wenli Li ◽  
Laura L. Hernandez
Keyword(s):  
Gene Expression ◽  
Mammary Gland ◽  
Differentially Expressed Genes ◽  
High Fat Diet ◽  
Differentially Expressed ◽  
Future Research ◽  
High Fat ◽  
Low Fat ◽  
Low Fat Diet ◽  
Positional Variation

Little attention has been given to the effect of positional variation of gene expression in the mammary gland. However, more research is shedding light regarding the physiological differences that mammary gland location can have on the murine mammary gland. Here we examined the differentially expressed genes between mammary gland positions under either a low-fat diet (LFD) or a high-fat diet (HFD) in the mid-lactation mammary gland (lactation day 11; L11). Three-week old WT C57BL/6 mice were randomly assigned to either a low-fat diet (LFD) or high fat diet (HFD) (n = 3/group) and either the right thoracic mammary gland (TMG) or inguinal mammary gland (IMG) was collected from each dam for a total of 12 unique glands. Within each diet, differentially expressed genes (DEGs) were first filtered by adjusted p-value (cutoff ≤ 0.05) and fold-change (FC, cutoff ≥2). Genes were further filtered by mean normalized read count with a cutoff≥10. We observed that mammary gland position had a significant impact on mammary gland gene expression with either LFD or HFD diet, with 1264 DEGs in LFD dams and 777 DEGs in HFD dams. We found that genes related to snRNP binding and translation initiation were most significantly altered between the TMG and IMG. Although we were not able to discern a molecular mechanism, many small nuclear RNAs and small nucleolar RNAs were differentially expressed between the TMG and IMG responsible for cellular functions such as splicing and ribosome biogenesis, which provides and interesting avenue for future research. Our study supports the hypothesis that collection of the mammary gland from a particular location influences mammary gland gene expression, thereby highlighting the importance for researchers to be vigilant in documenting and reporting which mammary gland they are using for their studies.

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