G0S2 functions as a tumor supressor through represssion of Myc signaling pathways
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE74696 | GEO | 2016/06/01
SECONDARY ACCESSION(S): PRJNA301170
REPOSITORIES: GEO
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Project description:Comparions on gene expression in murine embyonic fibroblasts (MEFs) wild-type vs G0S2 null MEFs Total RNA obtained from spontanously immortalized MEF cell line E2 from wild-type C57BL/6 mice (E2) and spontaneously immortalized MEF cell line E6 from G0S2 knockout C57BL/6 mice; MEF lines were used at passage number 10-12
2016-06-01 | E-GEOD-74696 | biostudies-arrayexpress
Project description:G0/G1 switch gene 2 (G0S2) is known to inhibit lipolysis through inhibition of adipose triglyceride lipase (ATGL). Although G0S2 has also been proposed to be involved in cancer progression, this role appears complex, and mechanisms are unclear. We recently reported a role for G0S2 in ER+ breast cancer suppression as low G0S2 expression correlated with increased recurrence after antiestrogen therapy and increased G0S2 expression sensitized ER+ breast cancer cells to tamoxifen and PI3K/mTOR inhibitors. In this report we dissect the role of G0S2 in ER+ versus ER- breast cancer. Overexpression of G0S2 in ER- breast cancer cells increased cell proliferation while G0S2 overexpression in ER+ breast cancer cells decreased cell proliferation. Transcriptome analysis revealed that G0S2 mediated distinct but overlapping transcriptional responses in ER- and ER+ cells. G0S2 reduced genes associated with an epithelial phenotype, especially in ER- cells, including CDH1, ELF3, STEAP4 and TACSTD2 suggesting promotion of the epithelial-mesenchymal transition (EMT). G0S2 also repressed estrogen signaling and estrogen receptor target gene signatures, especially in ER+ cells, including TFF1 and TFF3. In addition, G0S2 overexpression increased cell migration in ER- cells and increased estrogen deprivation sensitivity in ER+ cells. Interestingly, two genes downstream of ATGL in fat utilization, HMGCS1 and HMGCS2, that are also rate-limiting in steroid hormone biosynthesis, were downregulated in G0S2 overexpressing ER+ cells. In addition, HSD17B11, a gene that converts estradiol to its less estrogenic derivative, estrone, was highly upregulated in G0S2 overexpressing ER+ cells, suggesting G0S2 overexpression has a negative effect of estradiol production and maintenance. High levels of estrone were confirmed to be present in G0S2 overexpressing cells. High expression of G0S2 and HSD17B11 was associated with improved relapse free survival in breast cancer patients while high expression of HMGSC1 was associated with poor survival. In addition, the expression of G0S2 positively and negatively correlated respectively, with expression of HSD17B11 and HMGSC1 in patient samples. Finally, we deleted G0S2 in breast cancer prone MMTV-PyMT mice that have been hypothesized to be partially estrogen sensitive during early stages of tumorigenesis but develop ER- tumors. In this context, G0S2 functioned as a tumor promoter, with G0S2 null mice demonstrating a slight increase in tumor latency and decrease in tumor weight and a larger inhibitory effect on tumor metastasis. Our data indicates a complex role for G0S2 in breast cancer, dependent on ER status, that may be mediated in part by suppression of the estrogen signaling pathway.
2023-04-11 | GSE227698 | GEO
Project description:Hepatocellular carcinoma is the third leading cause of cancer death worldwide, and it is necessary to elucidate the mechanism of hepatocarcinogenesis. Circadian clock systems have been related in cell cycle and carcinogenesis. In this study, hepatocarcinogenesis induced by DEN administration in mice was inhibited by knockdown of G0s2 at early stage in carcinogenesis. In addition, the circadian expression of G0s2 in mouse liver was regulated by RARM-NM-1 controlled by clock genes and ATRA. Moreover, mice administered both ATRA and DEN were not induced hepatocellular carcinoma, and decreased the expression of G0s2 at second day after the initiation of administration. These findings suggest that the control of G0s2 expression is important in carcinogenesis and G0s2 might be the novel target for prevention, diagnosis and treatment of hepatocellular carcinoma. Differential gene expression between G0s2 siRNA or Control siRNA transfected primary hepatocyte was measured after 24 hr of transfection.
2013-08-01 | E-GEOD-39288 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma is the third leading cause of cancer death worldwide, and it is necessary to elucidate the mechanism of hepatocarcinogenesis. Circadian clock systems have been related in cell cycle and carcinogenesis. In this study, hepatocarcinogenesis induced by DEN administration in mice was inhibited by knockdown of G0s2 at early stage in carcinogenesis. In addition, the circadian expression of G0s2 in mouse liver was regulated by RARα controlled by clock genes and ATRA. Moreover, mice administered both ATRA and DEN were not induced hepatocellular carcinoma, and decreased the expression of G0s2 at second day after the initiation of administration. These findings suggest that the control of G0s2 expression is important in carcinogenesis and G0s2 might be the novel target for prevention, diagnosis and treatment of hepatocellular carcinoma.
2013-08-01 | GSE39288 | GEO
Project description:We identified 2 leading gene candidates (G0s2 and Rgs16) in response to circadian, diet and genetic manipulations by a large-scale transcriptome analysis. To examine the impact of G0s2 and Rgs16 on liver functions, we carried out adenovirus-mediated liver-specific knockdown of both genes and performed RNA-seq analysis.
2021-08-03 | GSE181262 | GEO
Project description:Background& Aims: The incidence of nonhepatitis B and nonhepatitis C viral (NBNC)- HCC has been rising in recent years due to the increase in NAFLD and NASH worldwide with fibrosis. However, the molecular mechanisms underlying the progression of these HCC are not fully understood. Here we observed that KDM6B, an H3K27 demethylase, was commonly downregulated in human NBNC-HCC and mouse NASH-related HCC by microarray analysis. The study aims to elucidate the molecular mechanism of KDM6B downregulation in NBNC-HCC including NASH-related HCC. Approach & Results: By immunohistochemistry, KDM6B expression was decreased in 28.7% of human HCC tissues, most of which were NBNC-HCC type. The low KDM6B expression group was accompanied by NASH in the adjacent liver. The KDM6B knockout (KO) HCC cells altered pathways of lipid metabolism by microarray and GSEA analysis. The KDM6B-KO cells significantly decreased lipid accumulation and cell reduction rates. Expression of two lipid-metabolism-related genes, G0S2 and ACSL1, were suppressed in the KDM6B-KO cells and the histone H3K27 trimethylation levels at the promoter regions were decreased when compared to the wild-type cells. Knockdown of G0S2 but not ACSL1 expression showed resistance to lipotoxicity in HCC cells. Moreover, inhibition of ATGL, a downstream target of G0S2, caused a decrease in lipid accumulation and cell proliferation. Conclusions: KDM6B regulates G0S2 expression via histone demethylation of its promoter region. Decreased KDM6B-dependent G0S2 expression through the histone modification pathway causes resistance to lipotoxicity, which may be involved in the carcinogenic mechanism of NASH-related HCC among NBNC-HCC.
2023-10-11 | GSE211848 | GEO
Project description:Current treatment for CML involves tyrosine kinase inhibitors (TKIs), which turned it into a managable disease. In a transcriptional profile of TKI-resistant versus newly diagnosed CML patient samples, G0S2 was shown to be profoundly downregulated.
2021-04-13 | GSE171945 | GEO
Project description:Effect of G0s2 and Rgs16 knockdown on hepatic transcriptome
| PRJNA751237 | ENA
Project description:Myc, a member of the Myc Network, supervises proliferation, metabolism and ribosomal function. The Mlx Network cross-talks with the Myc Network and regulates overlapping functions. We describe here the consequences of conditional Myc and/or Mlx gene knockouts (KOs) in primary and immortalized murine embryonic fibroblasts (MEFs). MycKO and MycKOxMlxKO “double KO” (DKO) primary MEFs, but not MlxKO MEFs, rapidly growth-arrested and displayed features of aging and senescence. In DKO MEFs, these were transient, indicating that Mlx was necessary to maintain them. KO MEFs deregulated transcripts pertaining to mitochondrial and ribosomal structure and function, cell cycle, aging, senescence and DNA damage. The expression of DNA damage-related proteins was also abnormal. Immortalized KO MEFs remained proliferation-competent but demonstrated differential sensitivities to genotoxic agents. Immortalized MycKO MEFs spontaneously developed tetraploidy that was Mlx-dependent. Different aspects of MEF aging, senescence and DNA damage responses are therefore differentially regulated by the Myc and Mlx Networks.
2023-08-28 | GSE210362 | GEO
Project description:Methylation-mediated silencing of G0-G1 switch gene 2 (G0S2) has been detected in a variety of solid tumors, whereas G0S2 induction is associated with remissions in patients with acute promyelocytic leukemia, implying that G0S2 may possess tumor suppressor activity. In this study, we clearly demonstrate that G0S2 opposes oncogene-induced transformation using G0s2-null immortalized mouse embryonic fibroblasts (MEF). G0s2-null MEFs were readily transformed with HRAS or EGFR treatment compared with wild-type MEFs. Importantly, restoration of G0S2 reversed HRAS-driven transformation. G0S2 is known to regulate fat metabolism by attenuating adipose triglyceride lipase (ATGL), but repression of oncogene-induced transformation by G0S2 was independent of ATGL inhibition. Gene expression analysis revealed an upregulation of gene signatures associated with transformation, proliferation, and MYC targets in G0s2-null MEFs. RNAi-mediated ablation and pharmacologic inhibition of MYC abrogated oncogene-induced transformation of G0s2-null MEFs. Furthermore, we found that G0S2 was highly expressed in normal breast tissues compared with malignant tissue. Intriguingly, high levels of G0S2 were also associated with a decrease in breast cancer recurrence rates, especially in estrogen receptor-positive subtypes, and overexpression of G0S2 repressed the proliferation of breast cancer cells in vitro. Taken together, these findings indicate that G0S2 functions as a tumor suppressor in part by opposing MYC activity, prompting further investigation of the mechanisms by which G0S2 silencing mediates MYC-induced oncogenesis in other malignancies.
| S-EPMC4775337 | biostudies-literature