Despite known age-related DNA methylation (aDNAm) changes in breast tumors, little is known about aDNAm in normal breast tissues. Breast tissues from a cross-sectional study of 121 cancer-free women, were assayed for genome-wide DNA methylation. mRNA expression was assayed by microarray technology. Analysis of covariance was used to identify aDNAms. Altered methylation was correlated with expression of the corresponding gene and with DNA methyltransferase protein DNMT3A, assayed by immunohistochemistry. Publically-available TCGA data were used for replication. 1,214 aDNAms were identified; 97% with increased methylation, and all on autosomes. Sites with increased methylation were predominantly in CpG lslands and non-enhancers. aDNAms with decreased methylation were generally located in intergenic regions, non-CpG Islands, and enhancers. Of the aDNAms identified, 650 are known to be involved in cancer, including ESR1 and beta-estradiol responsive genes. Expression of DNMT3A was positively associated with age. Two aDNAms showed significant associations with DNMT3A expression; KRR1 (OR 6.57, 95% CI: 2.51-17.23) and DHRS12 (OR 6.08, 95% CI: 2.33-15.86). A subset of aDNAms co-localized within vulnerable regions for somatic mutations in breast cancer. Expression of C19orf48 was inversely and significantly correlated with its methylation level. In the TCGA dataset, 84% and 64% of the previously identified aDNAms were correlated with age in both normal-adjacent and tumor breast tissues, with differential associations by histological subtype. Given the similarity of findings in the breast tissues of healthy women and breast tumors, and the effects on gene expression, aDNAms may be one pathway for increased breast cancer risk with age.
Landscape of genome-wide age-related DNA methylation in breast tissue.
Age, Race
View SamplesThis SuperSeries is composed of the SubSeries listed below.
LSD1 activates a lethal prostate cancer gene network independently of its demethylase function.
Specimen part, Cell line
View SamplesThe role of murine peroxisome proliferator-activated receptor-delta (PPARd) in mammary tumorigenesis was assessed. Microarrays were used to analyse global gene expression to determine changes in MMTV-PPARd transgenic mice versus wild-type mice and the effect of GW501516.
PPARδ induces estrogen receptor-positive mammary neoplasia through an inflammatory and metabolic phenotype linked to mTOR activation.
Specimen part, Treatment
View SamplesAfrican-American (AA) men experience increased risk of developing prostate cancers as well as increased mortality following treatment as compared to European-American (EA) men. The aim of our study was to identify biological factors with potential to predispose AA men to prostate tumor progression and metastasis.
Enhanced expression of SOS1 is detected in prostate cancer epithelial cells from African-American men.
No sample metadata fields
View SamplesWe performed a transcriptomic analysis to identify genes differentially transcribed in the maize stem upon corn borer feeding and treatment with insects regurgitates by using the MACE (Massive Analysis of cDNA Ends) technology. Overall design: Two comparisons were performed: Insect chewing vs control and Regurgitate+wounding vs wounding in three biological replicates per treatment
Maize Stem Response to Long-Term Attack by <i>Sesamia nonagrioides</i>.
Specimen part, Treatment, Subject
View SamplesOrganismal function is, to a great extent, determined by interactions among their fundamental building blocks, the cells. In?this work, we studied the cell-cell interactome of fetal placental trophoblast cells and maternal endometrial stromal cells, using single-cell transcriptomics. The placental interface mediates the interaction between two semiallogenic individuals, the mother and the fetus, and is thus the epitome of cell interactions. To study these, we inferred the cell-cell interactome? by assessing the gene expression of receptor-ligand pairs across cell types. Moreover, we find that the expression of G-protein coupled receptors is highly cell-type?specific, implying that ligand-receptor profiles could be a reliable tool for cell type identification. Furthermore, we find that uterine decidual cells represent a cell-cell interaction hub with a relatively large?number of potential incoming and outgoing signals. Decidual cells differentiate from their precursors, the endometrial stromal fibroblasts, during uterine preparation for pregnancy. We show that decidualization (even in vitro) enhances the ability ?to communicate with the fetus, as most of the receptors and ligands up-regulated during decidualization have their counterpart expressed in trophoblast cells. Among the signals transmitted, growth factors and immune signals dominate, suggesting a delicate balance of enhancing and suppressive signals. Finally, this study provides a rich resource of gene ?expression profiles of term intravillous and extravillous trophoblasts, including the transcriptome of the multinucleated syncytiotrophoblast. Overall design: We sequenced mRNA from primary human endometrial stromal fibroblasts and in vitro human decidualized stromal fibroblasts.
Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface.
Specimen part, Subject
View SamplesWe provide the tissue-level human placental transcriptomes from two term uncomplicated pregnancies. Tissue was collected at term C-section (no labor), from villous part of the placenta. Overall design: mRNA-seq of placenta from two term healthy pregnancies.
Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface.
Specimen part, Subject
View SamplesIn order to identify genes regulated by long noncoding RNA H19 in the ovary, we performed RNA-Seq with WT and H19KO ovaries from 8-week old mice. Among the differentially expressed genes, we found anti-mullerian hormone (AMH), which potentially plays an important role in regulating ovarian follicular development, might be a target of H19 mediated regulation. Overall design: Ovaries were harvested from 8-week old WT and H19KO mice, followed by total RNA extraction, library preparation and RNA-seq analysis to compare gene expression profiles between WT and H19KO conditions.
A novel, noncoding-RNA-mediated, post-transcriptional mechanism of anti-Mullerian hormone regulation by the H19/let-7 axis.
Age, Cell line, Subject
View SamplesDuplication of chromosomal arm 20q occurs in prostate, cervical, colon, gastric, bladder, melanoma, pancreas and breast cancer, suggesting that 20q amplification may play a key causal role in tumorigenesis. According to an alternative view, chromosomal instabilities are mainly a common side effect of cancer progression. To test whether a specific genomic aberration might serve as a cancer initiating event, we established an in vitro system that models the evolutionary process of early stages of prostate tumor formation; normal prostate cells were immortalized and cultured for 650 days till several transformation hallmarks were observed. Gene expression patterns were measured and chromosomal aberrations were monitored by spectral karyotype analysis at different times. Several chromosomal aberrations, in particular duplication of chromosomal arm 20q, occurred early in the process and were fixed in the cell populations, while other aberrations became extinct shortly after their appearance. A wide range of bioinformatic tools, applied to our data and to data from several cancer databases, revealed that spontaneous 20q amplification can promote cancer initiation. Our computational model suggests that deregulation of some key pathways, such as MAPK, p53, cell cycle regulation and Polycomb group factors, in addition to activation of several genes like Myc, AML, B-Catenin and the ETS family transcription factors, are key steps in cancer development driven by 20q amplification. Finally we identified 13 cancer initiating genes, located on 20q13, which were significantly overexpressed in many tumors, with expression levels correlated with tumor grade and outcome; these probably play key roles in inducing malignancy via20q amplification.
Amplification of the 20q chromosomal arm occurs early in tumorigenic transformation and may initiate cancer.
Specimen part
View SamplesWe used microarrays to characterize the global changes in gene expression in C2C12 cells due to siRNA knockdown of long non-coding RNA H19
The imprinted H19 lncRNA antagonizes let-7 microRNAs.
No sample metadata fields
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