27-Hydroxycholesterol, The Estrogen Receptor Modulator, Alters DNA Methylation in Breast Cancer

Vini, Ravindran; Rajavelu, Arumugam; Sreeja, Sreeharshan

doi:10.3389/fendo.2022.783823

Cited by 13 publications

(13 citation statements)

References 64 publications

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“…27-HC inhibits the uptake and synthesis of FA and cholesterol by inhibiting the SREBP pathway and activating the liver X receptor (LXR) pathway 106 . In contrast, 27-HC can competitively inhibit the effect of estrogen because of its selective estrogen receptor (ER) regulatory function and promotes the proliferation of high-ER-expressing tumor cells, such as breast and ovarian cancer cells 107 . It can also induce an increase in GPX4 expression, thereby protecting tumor cells from ferroptosis.…”

Section: Landscape Of Abnormal Lipid Metabolism In Tumorsmentioning

confidence: 99%

The role of lipid metabolic reprogramming in tumor microenvironment

Yang¹,

Wang²,

Song³

et al. 2023

Theranostics

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Metabolic reprogramming is one of the most important hallmarks of malignant tumors. Specifically, lipid metabolic reprogramming has marked impacts on cancer progression and therapeutic response by remodeling the tumor microenvironment (TME). In the past few decades, immunotherapy has revolutionized the treatment landscape for advanced cancers. Lipid metabolic reprogramming plays pivotal role in regulating the immune microenvironment and response to cancer immunotherapy. Here, we systematically reviewed the characteristics, mechanism, and role of lipid metabolic reprogramming in tumor and immune cells in the TME, appraised the effects of various cell death modes (specifically ferroptosis) on lipid metabolism, and summarized the antitumor therapies targeting lipid metabolism. Overall, lipid metabolic reprogramming has profound effects on cancer immunotherapy by regulating the immune microenvironment; therefore, targeting lipid metabolic reprogramming may lead to the development of innovative clinical applications including sensitizing immunotherapy.

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Section: Landscape Of Abnormal Lipid Metabolism In Tumorsmentioning

confidence: 99%

The role of lipid metabolic reprogramming in tumor microenvironment

Yang¹,

Wang²,

Song³

et al. 2023

Theranostics

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“…Nevertheless, whether aberrant epigenome contributes to 27‐HC–mediated cellular and morphological changes and breast cancer progression is unknown. We had earlier reported that 27‐HC induces DNA methylation changes in subsets of genes in breast cancer cells 17 . In this study, 27‐HC–mediated changes in histone methyltransferases in breast cancer cells were investigated.…”

Section: Introductionmentioning

confidence: 91%

27‐Hydroxycholesterol represses G9a expression via oestrogen receptor alpha in breast cancer

Vini,

Lekshmi,

Ravindran

et al. 2023

J Cellular Molecular Medi

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Abstract27‐hydroxycholesterol (27‐HC) is a cholesterol metabolite and the first discovered endogenous selective estrogen receptor modulator (SERM) that has been shown to have proliferative and metastatic activity in breast cancer. However, whether 27‐HC metabolite modulates the epigenetic signatures in breast cancer and its progression remains unclear. The current study, reports that 27‐HC represses the expression of euchromatic histone lysine methyltransferase G9a, further reducing di‐methylation at H3K9 in a subset of genes. We also observed reduced occupancy of ERα at the G9a promoter, indicating that 27‐HC negatively regulates the ERα occupancy on the G9a promoter and functions as a transcriptional repressor. Further, ChIP‐sequencing for the H3K9me2 mark has demonstrated that 27‐HC treatment reduces the H3K9me2 mark on subset of genes linked to cancer progression, proliferation, and metastasis. We observed upregulation of these genes following 27‐HC treatment which further confirms the loss of methylation at these genes. Immunohistochemical analysis with breast cancer patient tissues indicated a positive correlation between G9a expression and CYP7B1, a key enzyme of 27‐HC catabolism. Overall, this study reports that 27‐HC represses G9a expression via ERα and reduces the levels of H3K9me2 on a subset of genes, including the genes that aid in breast tumorigenesis and invasion further, increasing its expression in the breast cancer cells.

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“…As DNMT3b (de novo methyl transferase) methylates previously unmethylated sites, E2 may alter the methylation pattern at the promoter region of several genes and their expression during long-term memory formation. Several studies showed that E2 not only increased the expression of DNMT3b but also its activity (Vini et al, 2022 ). E2–ER complex recruits several chromatin modifiers such as histone deacetylase (HDAC) 1 and the repressor complex known as polycomb complex 2 (PRC2) at the ERE.…”

Section: E2-mediated Epigenetic Modificationsmentioning

confidence: 99%

Neuromodulating roles of estrogen and phytoestrogens in cognitive therapeutics through epigenetic modifications during aging

Singh

Paramanik²

2022

Front. Aging Neurosci.

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Estrogen (E2) plays important role in regulating hippocampal learning and memory. The decline of E2 after menopause affects learning and memory and increases the risk of neurodegenerative diseases like Alzheimer's disease (AD). Additionally, from the estrogen receptor (ER) mediated gene regulation; E2 also regulates gene expression at the transcriptional and posttranscriptional levels through epigenetic modifications. E2 recruits a number of proteins called co-regulators at the promoter region of genes. These co-regulators act as chromatin modifiers, alter DNA and histone modifications and regulate gene expression. Several studies show that E2 regulates learning and memory by altering chromatin at the promoters of memory-linked genes. Due to structural similarities with E2 and low side effects, phytoestrogens are now used as neuroprotective agents to recover learning and memory in animal models as well as human subjects during aging and different neurological disorders. Growing evidence suggests that apart from anti-oxidative and anti-inflammatory properties, phytoestrogens also act as epigenetic modifiers and regulate gene expression through epigenetic modifications. The epigenetic modifying properties of phytoestrogens are mostly studied in cancer cells but very little is known regarding the regulation of synaptic plasticity genes, learning and memory, and neurological disorders. In this article, we discuss the epigenetic modifying properties of E2 and the roles of phytoestrogens as epigenetic modifiers in the brain to recover and maintain cognitive functions.

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27-Hydroxycholesterol, The Estrogen Receptor Modulator, Alters DNA Methylation in Breast Cancer

Cited by 13 publications

References 64 publications

The role of lipid metabolic reprogramming in tumor microenvironment

The role of lipid metabolic reprogramming in tumor microenvironment

27‐Hydroxycholesterol represses G9a expression via oestrogen receptor alpha in breast cancer

Neuromodulating roles of estrogen and phytoestrogens in cognitive therapeutics through epigenetic modifications during aging

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