Article ; Online: Epigenetic Dysregulation and Its Correlation with the Steroidogenic Machinery Impacting Breast Pathogenesis: Data Mining and Molecular Insights into Therapeutics.
International journal of molecular sciences
2023 Volume 24, Issue 22
Abstract: Breast cancer (BC) is a heterogeneous condition and comprises molecularly distinct subtypes. An imbalance in the levels of epigenetic histone deacetylases (HDACs), modulating estrogen accumulation, especially 17β-estradiol (E2), promotes breast ... ...
Abstract | Breast cancer (BC) is a heterogeneous condition and comprises molecularly distinct subtypes. An imbalance in the levels of epigenetic histone deacetylases (HDACs), modulating estrogen accumulation, especially 17β-estradiol (E2), promotes breast tumorigenesis. In the present study, analyses of The Cancer Genome Atlas (TCGA) pan-cancer normalized RNA-Seq datasets revealed the dysregulation of 16 epigenetic enzymes (among a total of 18 members) in luminal BC subtypes, in comparison to their non-cancerous counterparts. Explicitly, genomic profiling of these epigenetic enzymes displayed increases in HDAC1, 2, 8, 10, 11, and Sirtuins (SIRTs) 6 and 7, and decreases in HDAC4-7, -9, and SIRT1-4 levels, respectively, in TCGA breast tumors. Kaplan-Meier plot analyses showed that these HDACs, with the exception of HDAC2 and SIRT2, were not correlated with the overall survival of BC patients. Additionally, disruption of the epigenetic signaling in TCGA BC subtypes, as assessed using both heatmaps and boxplots, was associated with the genomic expression of factors that are instrumental for cholesterol trafficking/utilization for accelerating estrogen/E2 levels, in which steroidogenic acute regulatory protein (STAR) mediates the rate-limiting step in steroid biosynthesis. TCGA breast samples showed diverse expression patterns of a variety of key steroidogenic markers and hormone receptors, including |
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MeSH term(s) | Humans ; Female ; Epigenomics ; Breast Neoplasms/pathology ; Estrogens/therapeutic use ; Data Mining ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic |
Chemical Substances | Estrogens |
Language | English |
Publishing date | 2023-11-18 |
Publishing country | Switzerland |
Document type | Journal Article |
ZDB-ID | 2019364-6 |
ISSN | 1422-0067 ; 1422-0067 ; 1661-6596 |
ISSN (online) | 1422-0067 |
ISSN | 1422-0067 ; 1661-6596 |
DOI | 10.3390/ijms242216488 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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