Sequencing of chronic myeloid leukemia (CML) cell lines upon upregulation or downregulation of G0/G1 switch gene (G0S2)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA721438 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14217412_1.fastq.gz | Fastqsanger.gz | |||
| SRR14217412_2.fastq.gz | Fastqsanger.gz | |||
| SRR14217413_1.fastq.gz | Fastqsanger.gz | |||
| SRR14217413_2.fastq.gz | Fastqsanger.gz | |||
| SRR14217414_1.fastq.gz | Fastqsanger.gz |
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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:Abnormal blood vessel growth in the eye is a leading cause of vision loss globally, particularly in diseases like diabetic retinopathy where the vitreous plays a crucial but poorly understood role in disease progression. While we know the vitreous can stimulate blood vessel growth, the specific molecular mechanisms remain unclear. Here we show that a protein called G0S2 (G0/G1 switch gene 2) serves as a key regulator of blood vessel growth in response to normal vitreous. Through comprehensive gene analysis, we discovered that G0S2 levels increase significantly when blood vessel cells are exposed to normal vitreous. The importance of G0S2 is highlighted by our finding that uveal melanoma patients with higher G0S2 levels had poorer survival rates. When we removed G0S2 from blood vessel cells, they no longer responded to vitreous stimulation, confirming its critical role. Notably, we identified an existing drug that can target G0S2, potentially offering a new therapeutic approach. This discovery of G0S2's role and its potential therapeutic targeting opens new avenues for treating eye diseases characterized by abnormal blood vessel growth, while also providing a valuable biomarker for predicting disease progression in eye cancer patients
2025-03-03 | GSE289206 | GEO
Project description:Abnormal blood vessel growth in the eye is a leading cause of vision loss globally, particularly in diseases like diabetic retinopathy where the vitreous plays a crucial but poorly understood role in disease progression. While we know the vitreous can stimulate blood vessel growth, the specific molecular mechanisms remain unclear. Here we show that a protein called G0S2 (G0/G1 switch gene 2) serves as a key regulator of blood vessel growth in response to normal vitreous. Through comprehensive gene analysis, we discovered that G0S2 levels increase significantly when blood vessel cells are exposed to normal vitreous. The importance of G0S2 is highlighted by our finding that uveal melanoma patients with higher G0S2 levels had poorer survival rates. When we removed G0S2 from blood vessel cells, they no longer responded to vitreous stimulation, confirming its critical role. Notably, we identified an existing drug that can target G0S2, potentially offering a new therapeutic approach. This discovery of G0S2's role and its potential therapeutic targeting opens new avenues for treating eye diseases characterized by abnormal blood vessel growth, while also providing a valuable biomarker for predicting disease progression in eye cancer patients
2025-03-03 | GSE289204 | GEO
Project description:Tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 have turned chronic myeloid leukaemia (CML) from a fatal disease into a manageable condition for most patients. Despite improved survival, targeting drug-resistant leukaemia stem cells (LSCs) remains a challenge for curative CML therapy. Aberrant lipid metabolism can have a large impact on membrane dynamics, cell survival and therapeutic responses in cancer. While ceramide and sphingolipid levels were previously correlated with TKI response in CML, the role of lipid metabolism in TKI resistance is not well understood. We have identified downregulation of a critical regulator of lipid metabolism, G0/G1 switch gene 2 (G0S2), in multiple scenarios of TKI resistance, including (1) BCR::ABL1 kinase-independent TKI resistance, (2) progression of CML from the chronic to the blast phase of the disease, and (3) in CML versus normal myeloid progenitors. Accordingly, CML patients with low G0S2 expression levels had a worse overall survival. G0S2 downregulation in CML was not a result of promoter hypermethylation or BCR::ABL1 kinase activity, but was rather due to transcriptional repression by MYC. Using CML cell lines, patient samples and G0s2 knockout (G0s2-/- ) mice, we demonstrate a tumour suppressor role for G0S2 in CML and TKI resistance. Our data suggest that reduced G0S2 protein expression in CML disrupts glycerophospholipid metabolism, correlating with a block of differentiation that renders CML cells resistant to therapy. Altogether, our data unravel a new role for G0S2 in regulating myeloid differentiation and TKI response in CML, and suggest that restoring G0S2 may have clinical utility.
| S-EPMC9763536 | biostudies-literature
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:NIH3T3 in the middle of G0 to G1 transion consists of the cells which is still staying G0 phase and the cells which enters G1. Monitoring the expressions of p27 and Cdt1 enables to distinguish these two; p27+/Cdt1+ cells as the cells in G0 phase and p27-Cdt1+ cells as G1 phase We sorted p27+Cdt1+ (G0) NIH3T3 cells and p27-Cdt1+ (G1) NIH3T3 cells in the middle of G0-G1 transition, 5 hours after serum addition following the serum addition using mVenus-p27K- and mCherry-hCdt1(30/120) . We compared the expression profiles of these NIH3T3 cells in G0 and G1 phases and identified the genes upregulated in G0 or G1 phases.
2014-02-21 | GSE46511 | GEO
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:NIH3T3 in the middle of G0 to G1 transion consists of the cells which is still staying G0 phase and the cells which enters G1. Monitoring the expressions of p27 and Cdt1 enables to distinguish these two; p27+/Cdt1+ cells as the cells in G0 phase and p27-Cdt1+ cells as G1 phase We sorted p27+Cdt1+ (G0) NIH3T3 cells and p27-Cdt1+ (G1) NIH3T3 cells in the middle of G0-G1 transition, 5 hours after serum addition following the serum addition using mVenus-p27K- and mCherry-hCdt1(30/120) . We compared the expression profiles of these NIH3T3 cells in G0 and G1 phases and identified the genes upregulated in G0 or G1 phases. The p27+Cdt1+ (G0) NIH3T3 cells and p27-Cdt1+ (G1) NIH3T3 cells were sorted by FACS for RNA extraction and hybridization on Affymetrix microarrays.
2014-02-21 | E-GEOD-46511 | 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 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