Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hyperpolarization-Activated Cyclic Nucleotide-Gated Potassium Channel 3 Promotes HCC Development in a Female-biased Manner

ABSTRACT: Sex differences in hepatocellular carcinoma (HCC) development are regulated by sex and non-sex chromosomes, sex hormones, and environmental factors. We previously reported that Ncoa5+/- mice develop HCC in a male-biased manner. Here we show that NCOA5 expression was reduced in male patient HCCs while the expression of an NCOA5-interacting tumor suppressor, TIP30, was lower in female HCCs. Tip30 heterozygous deletion did not change HCC incidence in Ncoa5+/- male mice but dramatically increased HCC incidence in Ncoa5+/- female mice, accompanied by hepatic hyperpolarization-activated cyclic nucleotide-gated cation channel 3 (HCN3) overexpression. HCN3 overexpression cooperated with MYC to promote mouse HCC development, whereas Hcn3 knockout preferentially hindered HCC development in female mice. Furthermore, HCN3 amplification and overexpression occurred in human HCCs and correlated with a poorer prognosis of patients in a female-biased manner. Our results suggest that TIP30 and NCOA5 protect against female liver oncogenesis and that HCN3 is a female-biased HCC driver.

ORGANISM(S): Mus musculus

PROVIDER: GSE228531 | GEO | 2023/08/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Julidochromis species male vs. female 20100721

Project description:Whole brain gene expression profiling for Julidochromis transcriptus male vs. female and Julidochromis marlieri male vs female to identify sex-role biased and sex biased gene expression in these species that exhibit conventional and reversed sex-biased behavior respectively.

2010-07-24 | GSE23094 | GEO

Genome-wide maps of histone modifications in male and female mouse liver

Project description:Here we map six chromatin modifications -- H3K4me1, H3K4me3, H3K27ac, H3K36me3, H3K9me3, and H3K27me3 -- genome-wide in male and female mouse liver in order to identify histone modifications that characterize sex-biased genes and sex-biased DNase hypersensitive sites and their regulation by plasma growth hormone (GH) profiles, which are sexually dimorphic. We find distinct mechanisms of regulation in male liver and female liver: sex-dependent K27me3-mediated repression is an important mechanism of repression of female-biased, but not of male-biased, genes, and a sex-dependent K4me1 distribution, suggesting nucleosome repositioning by pioneer factors, is observed at male-biased, but not female-biased, regulatory sites. STAT5-mediated activation is most strongly associated with sex-biased chromatin modifications, while BCL6-mediated repression primarily occurs in association with sex-independent chromatin modifications, both at binding sites and at target genes. These samples are part of a study on chromatin states in male and female mouse and their role in sex-biased liver gene expression (A Sugathan and DJ Waxman (2013) Molec Cell Biol).

2013-07-03 | GSE44571 | GEO

RNA-seq gene expression profiling of livers from CD1 mice treated with adeno-associated virus encoding constitutively active STAT5b (AAV8-STAT5ca)

Project description:PolyA-selected nuclear RNA isolated from livers of adult male mice administered AAV8-STAT5ca was analyzed by RNA-seq to determine the impact of constitutive STAT5 activation on the expression of sex-biased genes in male mouse liver. This is part of a study entitled 'Constitutively active STAT5b feminizes mouse liver gene expression', where delivery of constitutively active STAT5 (STAT5CA) to male mouse liver was shown to induce widespread feminization of the liver, with extensive induction of female-biased genes and repression of male-biased genes, largely mimicking results obtained when male mice are given GH as a continuous infusion. Many of the STAT5CA-responding genes were associated with nearby (< 50 kb) sites of STAT5 binding to liver chromatin, supporting the proposed direct role of persistently active STAT5 in continuous GH-induced liver feminization. The feminizing effects of STAT5CA were dose-dependent; moreover, at higher levels, STAT5CA overexpression resulted in some histopathology, including hepatocyte hyperplasia, and increased karyomegaly and multinuclear hepatocytes. Together, these findings establish that the persistent activation of STAT5 by GH that characterizes female liver is by itself sufficient to account for the sex-dependent expression of a majority of hepatic sex-biased genes.

2022-04-04 | GSE196015 | GEO

RNA-seq gene expression profiling of livers from C57Bl/6 mice treated with adeno-associated virus encoding constitutively active STAT5b (AAV8-STAT5ca)

Project description:PolyA-selected total RNA isolated from livers of adult male mice administered AAV8-STAT5ca was analyzed by RNA-seq to determine the impact of constitutive STAT5 activation on the expression of sex-biased genes in male mouse liver. This is part of a study entitled 'Constitutively active STAT5b feminizes mouse liver gene expression', where delivery of constitutively active STAT5 (STAT5CA) to male mouse liver was shown to induce widespread feminization of the liver, with extensive induction of female-biased genes and repression of male-biased genes, largely mimicking results obtained when male mice are given GH as a continuous infusion. Many of the STAT5CA-responding genes were associated with nearby (< 50 kb) sites of STAT5 binding to liver chromatin, supporting the proposed direct role of persistently active STAT5 in continuous GH-induced liver feminization. The feminizing effects of STAT5CA were dose-dependent; moreover, at higher levels, STAT5CA overexpression resulted in some histopathology, including hepatocyte hyperplasia, and increased karyomegaly and multinuclear hepatocytes. Together, these findings establish that the persistent activation of STAT5 by GH that characterizes female liver is by itself sufficient to account for the sex-dependent expression of a majority of hepatic sex-biased genes.

2022-04-04 | GSE196014 | GEO

Prediction of sex-determination mechanisms in avian primordial germ cells using RNA-seq analysis

Project description:Avian sex is determined by various factors, such as the dosage of DMRT1 and cell-autonomous mechanisms. While the sex-determination mechanism in gonads is well analyzed, the mechanism in germ cells remains unclear. In this study, we explored the gene expression profiles of male and female primordial germ cells (PGCs) during embryogenesis in chickens to predict the mechanism of sex-determination. Male and female PGCs were isolated from blood and gonads with a purity > 96% using flow cytometry and analyzed using RNA-seq. Prior to settlement in the gonads, female circulating PGCs (cPGCs) obtained from blood displayed sex-biased expression. Gonadal PGCs (gPGCs) also displayed sex-biased expression, and the number of female-biased genes detected was higher than male-biased genes. The female-biased genes in gPGCs were enriched in some metabolic processes. To reveal the mechanisms underlying the transcriptional regulation of female-biased genes in gPGCs, we performed stimulation tests. Stimulation with retinoic acid against cultured gPGCs derived from male embryos resulted in the upregulation of several female-biased genes. Overall, our results suggest that sex determination of avian PGCs possess aspects of both cell-autonomous and somatic cell regulation. Moreover, it appears that sex determination occurs earlier in females than in males.

2022-02-24 | GSE188689 | GEO

Small RNA-seq of adult male and female mouse liver

Project description:Total RNA-seq analysis of mouse liver RNA following locked nucleic acids (LNAs) treatment to identify mRNA targets of mmu-miR-802-5p and mmu-miR-1948-5p in vivo. These datasets are part of a study where we used small RNA sequencing to discover 24 sex-biased mouse liver miRNAs, and then investigated the roles of two of these miRNAs in GH-regulated liver sex differences. Studies in pre-pubertal and young adult mice, and in mice where pituitary hormones are ablated or where sex-specific hepatic GH signaling is dysregulated, demonstrated that the male-biased miR-1948 and the female-biased miR-802 are both regulated by sex-specific pituitary GH secretory patterns, acquire sex specificity at puberty, and are dependent on the GH-activated transcription factor STAT5 for their sex-specific expression. Both miRNAs are within genomic regions characterized by sex-biased chromatin accessibility. miR-1948, a novel, uncharacterized miRNA, has essential features for correct Drosha/Dicer processing, generates a bona fide mature miRNA with strong strand bias for the 5p arm, and is bound by Argonaute in liver tissue, as is miR-802. In vivo studies using inhibitory locked nucleic acid sequences revealed that miR-1948-5p preferentially represses female-biased mRNAs and induces male-biased mRNAs in male liver, and conversely, miR-802-5p preferentially represses male-biased mRNAs and increases levels of female-biased mRNAs in female liver. Cytochrome P450 mRNAs were strongly enriched as targets of both miRNAs. Thus, miR-1948-5p and miR-802-5p are functional components of the GH regulatory network that shapes sex-differential gene expression in mouse liver.

2018-01-25 | GSE103879 | GEO

Single-nucleus RNA-seq of adult female and male mouse livers for sex-biased gene expression analyses

Project description:To obtain new insight into the sexual dimorphism of mammalian livers, single-nucleus RNA-seq was performed on the liver samples from two female and two male adult mice. The single-nucleus libraries were generated on the 10X Chromium Next GEM Single Cell 3ʹ platform and sequenced on Illumina NextSeq 550. We used the data to understand the heterogeneity and sex-biased gene expression of liver cell types. The data revealed significant sex differences primarily focused on hepatocytes. Specifically, from the sex-biased genes detected at the bulk tissue level, we observed that male-biased genes are more highly expressed in male hepatocytes, and female-biased genes are more highly expressed in female hepatocytes.

2023-08-03 | E-MTAB-12180 | biostudies-arrayexpress

Genome-wide maps of histone modifications in male and female mouse liver

2013-07-03 | E-GEOD-44571 | biostudies-arrayexpress

Identification of Hnf6 binding sites in male and female mouse liver

Project description:∼40,000 HNF6 binding sites were identified in mouse liver chromatin, including several thousand sites showing significant differences in level of HNF6 binding between male and female mouse liver. These sex-biased HNF6 binding sites showed strong enrichment for sex-biased DNase hypersensitive sites and for proximity to genes showing local sex-biased chromatin marks and a corresponding sex-biased expression. ~90% of genome-wide CUX2 binding sites identified previously in female mouse liver (Conforto TL, Zhang Y, Sherman J, Waxman DJ., Mol Cell Biol. 2012;32(22):4611-4627) were also bound by HNF6, giving evidence for genome-wide competition between HNF6 and CUX2 for chromatin binding in female mouse liver. These HNF6/CUX2 common binding sites were enriched for genomic regions more accessible in male than in female mouse liver chromatin, and showed strongest enrichment for male-biased genes, suggesting HNF6 displacement by CUX2 as a mechanism to explain the observed CUX2 repression of male-biased genes in female liver. However, HNF6 binding was sex-independent at a majority of its binding sites, and peak regions of HNF6 binding were frequently associated with co-binding by multiple other liver transcription factors, consistent with HNF6 playing a global regulatory role in both male and female liver.

2015-07-28 | GSE60014 | GEO

Identification of Hnf6 binding sites in male and female mouse liver

2015-07-28 | E-GEOD-60014 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data