Effect of ovariectomy and LCAT overexpression on gene expression of mouse liver cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE255753 | GEO | 2024/02/19
REPOSITORIES: GEO
Similar Datasets
Project description:Liver cancer exhibits significant gender disparities, with men having a 2-5 times higher risk of developing liver cancer compared to women. Numerous studies have demonstrated the influence of estrogen on liver cancer development, although the precise underlying mechanism remains unclear. Peroxiredoxins (PRDXs) represent a recently identified peroxidase family that modulates various signaling pathways associated with reactive oxygen species. This research aims to explore the impact of estrogen on the expression of PRDX1, PRDX5, and PRDX6 in hepatocellular carcinoma cells, thereby modulating liver cancer progression. Treatment with estrogen and the silencing of PRDX1, PRDX5, and PRDX6 impairs the proliferative capacity of hepatocarcinoma cells. The levels of PRDX1, PRDX5, and PRDX6 were found to be elevated in hepatocellular carcinoma compared to normal tissues, with estrogen demonstrating the ability to decrease their expression in hepatocellular carcinoma cells. Furthermore, estrogen influences the expression of PRDXs (PRDX5 and PRDX6) by regulating RASA1. Additionally, estrogen stimulation impacts ferroptosis in hepatocellular carcinoma cells, suggesting that PRDXs and ferroptosis-related genes are estrogen-responsive genes that promote liver cancer progression. Elevated LPCAT3 levels and downregulation of PRDX1, PRDX5, and PRDX6 expression may potentially manage the advancement of HCC.
2024-08-26 | PXD055317 |
Project description:The loss of skeletal muscle strength mid-life in females is associated with the decline of estrogen. Here, we questioned how estrogen deficiency might impact the overall skeletal muscle phosphoproteome after contraction, as force production induces phosphorylation of several muscle proteins. Phosphoproteomic analyses of the tibialis anterior muscle after contraction in two mouse models of estrogen deficiency, ovariectomy (Ovariectomized [Ovx] vs Sham) and natural aging-induced ovarian senescence (Older Adult [OA] vs Young Adult [YA]), identified a total of 2,593 and 3,507 phosphopeptides in Ovx/Sham and OA/YA datasets, respectively. Further analysis of estrogen deficiency-associated proteins and phosphosites identified 66 proteins and 21 phosphosites from both datasets. Of these, 4 estrogen deficiency-associated proteins and 4 estrogen deficiency-associated phosphosites were significant and differentially phosphorylated or regulated, respectively. Comparative analyses between Ovx/Sham and OA/YA using Ingenuity Pathway Analysis (IPA) found parallel patterns of inhibition and activation across IPA-defined canonical signaling pathways and physiological functional analysis, which were similarly observed in downstream GO, KEGG, and Reactome pathway overrepresentation analysis pertaining to muscle structural integrity and contraction, including AMPK and calcium signaling. IPA Upstream regulator analysis identified MAPK1 and PRKACA as candidate kinases and calcineurin as a candidate phosphatase sensitive to estrogen. Our findings highlight key molecular signatures and pathways in contracted muscle suggesting that the similarities identified across both datasets could elucidate molecular mechanisms that may contribute to skeletal muscle strength loss due to estrogen deficiency.
2023-09-01 | PXD035171 | Pride
Project description:Liver cancer is a common cause of cancer death, with a male-predominant incidence due, in part, to increased estrogen levels in cirrhotic patients. It is unknown, however, how estrogen is sensed to influence this process. Here, we show that estrogen activates the G protein-coupled estrogen receptor 1 (GPER1), expressed in hepatocytes, to enhancing hepatocyte size, cell cycle progression and cell proliferation, thereby increasing liver growth in zebrafish larvae and adults. GPER1 stimulation activates PI3K/mTOR signaling, and mTOR is essential for both normal and regenerative organ growth. Genetic loss of GPER1 diminishes and estrogen exposure accelerates chemical carcinogenesis, specifically in males. Chemical inhibition of GPER1 significantly reduces cancer incidence and progression in a gender-specific fashion. Our studies identify GPER1 as a hepatic estrogen sensor that mediates gender dimorphic growth, mTOR activation, and can serve as a therapeutic target for liver cancer treatment.
2019-05-29 | GSE92544 | GEO
Project description:Pathway preferential estrogen 1 (PaPE-1) is a novel estrogen receptor ligand that has been shown to favorably affect metabolic tissues without adverse effects on reproductive tissues. In this study, we have examined the effects of PaPE-1 on metabolic health, in particular, examin-ing its effects on the liver transcriptome and on plasma metabolites in two different mouse mod-els: diet-induced obesity (DIO) and leptin-deficient (ob/ob) mice. PaPE-1 significantly decreased liver weight and lipid accumulation in both DIO and ob/ob models and lowered the expression of genes associated with fatty acid metabolism and collagen deposition. Overall, our findings support a beneficial metabolic role for PaPE-1 and suggest that PaPE-1 may protect postmenopausal women from fatty liver disease without increasing reproductive cancer risk.
2024-08-10 | GSE181780 | GEO
Project description:Estrogen rescues the loss of gas exchange units in ovariectomized mice. This project studies the mechanisms of this rescue in ovariectomized mice treated with or without estrogen. Keywords: other
2004-04-14 | GSE1303 | GEO
Project description:To search for the role of microRNAs in postmenopausal osteoporosis, we used an experimental ovariectomized (OVX) mice moldel. We operated ovariectomy in 3-month-old C57BL/6 mice and collected the femurs after 6months to perform miRNA microarray analysis to identify dysregulated microRNAs.
2018-01-27 | GSE109705 | GEO
Project description:Historically, lower incidence of CVD and related deaths in women compared to men of the same age has been attributed to female sex hormones, particularly estrogen and its receptors. Autologous Bone marrow stem cell (BMSC) clinical trials for cardiac cell therapy overwhelmingly included male patients; however, meta-analysis data on these trials suggest a better functional outcome in women compared to men. Direct comparison of gender-specific cardiac reparative activity and estrogen-independent mechanisms that regulate gender-specific dimorphisms of BMSC has not been studied. This study was designed to identify sex hormone-independent mechanisms that regulate superior reparative properties of female endothelial progenitor cells (EPCs) post-MI, particularly epigenetic mechanisms. Male (M), female (F), and ovariectomized female (OVX) mice-derived EPCs were subjected to a series of molecular and epigenetic analyses followed by in vivo functional assessments of cardiac repair. RNA sequencing and other quantitative assays showed a similar genetic profile between F-EPCs and OVX-EPCs, distinct from M-EPCs that displayed significant up-regulation of inflammation-related genes. F-EPCs and OVX EPCs secrete higher levels of proangiogenic factors, lower levels of proinflammatory cytokines and show better cardiac reparative activity after intra-cardiac injections in a male mouse model of myocardial infarction (MI). Epigenetic sequencing revealed a marked difference in the occupancy of the gene repressive H3K9me3 mark, particularly at transcription start sites of key angiogenic and proinflammatory genes in male EPCs compared to female and ovariectomized EPCs. Our study unveiled that functional gender dimorphism in EPCs is, in part, mediated by differential epigenetic regulation of the proinflammatory and anti-angiogenic gene CCL3, orchestrated by the control of H3K9me3 by histone methyltransferase, G9a/Ehmt2. Our research highlights the importance of considering gender of donor cells for progenitor based tissue repair.
2024-01-30 | GSE253057 | GEO
Project description:Historically, lower incidence of CVD and related deaths in women compared to men of the same age has been attributed to female sex hormones, particularly estrogen and its receptors. Autologous Bone marrow stem cell (BMSC) clinical trials for cardiac cell therapy overwhelmingly included male patients; however, meta-analysis data on these trials suggest a better functional outcome in women compared to men. Direct comparison of gender-specific cardiac reparative activity and estrogen-independent mechanisms that regulate gender-specific dimorphisms of BMSC has not been studied. This study was designed to identify sex hormone-independent mechanisms that regulate superior reparative properties of female endothelial progenitor cells (EPCs) post-MI, particularly epigenetic mechanisms. Male (M), female (F), and ovariectomized female (OVX) mice-derived EPCs were subjected to a series of molecular and epigenetic analyses followed by in vivo functional assessments of cardiac repair. RNA sequencing and other quantitative assays showed a similar genetic profile between F-EPCs and OVX-EPCs, distinct from M-EPCs that displayed significant up-regulation of inflammation-related genes. F-EPCs and OVX EPCs secrete higher levels of proangiogenic factors, lower levels of proinflammatory cytokines and show better cardiac reparative activity after intra-cardiac injections in a male mouse model of myocardial infarction (MI). Epigenetic sequencing revealed a marked difference in the occupancy of the gene repressive H3K9me3 mark, particularly at transcription start sites of key angiogenic and proinflammatory genes in male EPCs compared to female and ovariectomized EPCs. Our study unveiled that functional gender dimorphism in EPCs is, in part, mediated by differential epigenetic regulation of the proinflammatory and anti-angiogenic gene CCL3, orchestrated by the control of H3K9me3 by histone methyltransferase, G9a/Ehmt2. Our research highlights the importance of considering gender of donor cells for progenitor based tissue repair.
2024-01-30 | GSE252946 | GEO
Project description:The peri- and postmenopausal periods in women are associated with decreases in circulating estrogen levels, marked acceleration of age-related bone loss and increased risk of fracture. However, despite the clinical importance of postmenopausal bone loss, our molecular understanding of this process is incomplete. Here, we used co-expression network analysis to gain novel insight into the molecular mechanisms mediating bone loss in ovariectomized (OVX) mice, a model of human menopause. Expression profiles from intact and OVX mice from a panel of inbred strains were used to generate a co-expression network consisting of 29 modules. Genes in network module 25 were decreased by OVX in all strains. Module 25 was enriched for genes involved in the response to oxidative stress, a process known to be an upstream causal factor for OVX-induced bone loss. It was also found that module 25 homologs were co-expressed in human bone marrow and were enriched for genes with evidence of genetic association with bone mineral density (BMD) in women. Alpha synuclein (Snca) was the most highly connected “hub” genes in module 25 and its in vivo knockout resulted in a 40% reduction in OVX-induced bone loss. Furthermore, protection was associated with the targeted alteration of genes in specific network modules, including module 10. Our results identify a gene module associated with OVX-induced bone loss and demonstrate that Snca regulates ovariectomy-induced bone loss by controlling bone network dynamics.
2016-12-01 | GSE68303 | GEO
Project description:Membrane estrogen receptor (ER) alpha stimulates AMP kinase to suppress SREBP1 processing and lipids in liver Here we present evidence that signaling from membrane-localized ERalpha similarly suppresses a subset of mRNAs in the livers of female WT and membrane only estrogen receptor (MOER) transgenic mice but not in estrogen receptor knock out (ERKO) mice Three month old wild type, MOER and ERKO mice were ovariectomized and utilized per IRB-approved. Following ovariectomy and recovery the animals were injected intraperitoneally with PPT (100 ?g) or oil placebo (0.1 mL) daily for 3 days. Whole livers were removed upon euthanasia.
2013-05-14 | E-GEOD-45346 | biostudies-arrayexpress