Regulation of TERT and HKR3 in Hep3B cell lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE135581 | GEO | 2019/08/09
REPOSITORIES: GEO
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Project description:Regulation of TERT and HKR3 in Hep3B cell lines
| PRJNA559360 | ENA
Project description:Using microcell-mediated chromosome transfer (MMCT) into the mouse melanoma cell line, B16F10, we have previously found that human chromosome 5 carries a gene, or genes, that can negatively regulate TERT expression. To identify the gene responsible for the regulation of TERT transcription, we performed cDNA microarray analysis using parental B16F10 cells, telomerase negative B16F10 microcell hybrids with a human chromosome 5 (B16F10MH5), and its revertant clones (MH5R) with reactivated telomerase. Here we report the identification of PITX1, whose restoration leads to the downregulation of mouse tert (mtert) transcription, as a TERT suppressor gene. Additionally, both human TERT (hTERT) and mouse TERT (mtert) promoter activity can be suppressed by PITX1. We showed that three and one binding sites, respectively, within the hTERT and mtert promoters that express a unique conserved region are responsible for the transcriptional activation of TERT. Furthermore, we showed that PITX1 binds to the TERT promoter both in vitro and in vivo. Thus, PITX1 suppresses TERT transcription through direct binding to the TERT promoter, which ultimately regulates telomerase activity.
2010-09-10 | GSE23216 | GEO
Project description:Using microcell-mediated chromosome transfer (MMCT) into the mouse melanoma cell line, B16F10, we have previously found that human chromosome 5 carries a gene, or genes, that can negatively regulate TERT expression. To identify the gene responsible for the regulation of TERT transcription, we performed cDNA microarray analysis using parental B16F10 cells, telomerase negative B16F10 microcell hybrids with a human chromosome 5 (B16F10MH5), and its revertant clones (MH5R) with reactivated telomerase. Here we report the identification of PITX1, whose restoration leads to the downregulation of mouse tert (mtert) transcription, as a TERT suppressor gene. Additionally, both human TERT (hTERT) and mouse TERT (mtert) promoter activity can be suppressed by PITX1. We showed that three and one binding sites, respectively, within the hTERT and mtert promoters that express a unique conserved region are responsible for the transcriptional activation of TERT. Furthermore, we showed that PITX1 binds to the TERT promoter both in vitro and in vivo. Thus, PITX1 suppresses TERT transcription through direct binding to the TERT promoter, which ultimately regulates telomerase activity. We transferred intact human chromosome 5 into mouse melanoma B16F10 cells by microcell fusion. The microcell hybrids (MH5) exhibited suppression of telomerase, we also obtained revertant clones (MH5R) in which telomerase is reactivated. To identify the differentially expressed genes on human chromosome 5, we performed expression microarray analysis using these two clones and parental B16F10 cells.
2010-09-10 | E-GEOD-23216 | biostudies-arrayexpress
Project description:Transcriptional re-activation of hTERT is the limiting step in tumorigenesis. While mutations in hTERT promoter seen in 19% of all cancers are recognized as key drivers of hTERT reactivation, mechanisms by which the wildtype hTERT (WT-hTERT) promoter is reactivated, as observed in the majority of cancers, remain unknown. We report that unlike with the mutant-hTERT promoters, a T-INT2 (Tert INTeracting region 2) region located ~120kb upstream of the hTERT proximal promoter is essential to uniquely reactivate the WT-hTERT promoter, via long-range chromatin interactions. Unlike mutant-hTERT promoters, which are driven by GABPa/b tetramers tethered between T-INT1 (Tert-INTeracting-region 1) and de-novo ETS sites created by promoter mutations, WT-hTERT promoter firing is initiated by 2 events a) elevated JunD mediated recruitment of CTCF and b) β-catenin and CBP mediated recruitment of Sp1 tetramers between T-INT2 and WT-hTERT proximal-promoter, leading to chromatin-openness, pol2 recruitment and productive transcription.
2023-01-08 | GSE163069 | GEO
Project description:Overexpression of SOX4 in various kinds of cancers specimen was associated with poor prognosis of patients; however, the role of SOX4 in angiogenesis or tumor microenvironment modulation remains unclear. Therefore the endogenous SOX4 was knockout and the differential gene expression between Hep3B and Hep3B SOX4-/- cells were examined via genechip. We found that the differentially expressed genes, EzH2, a SOX4-associated partner, and CXCL12, were repressed in Hep3B SOX4-/- cells compared with parental Hep3B; these results were further assessed via qRT-PCR in Hep3B SOX4-/- versus Hep3B cells.
2020-12-01 | GSE141909 | GEO
Project description:In this study, we investigated the biological roles and potential mechanisms of pentamethylquercetin (PMQ), a natural polymethyl flavones, against Hep3B liver cancer cells. Cell viability and growth curves were determined using the cell counting kit-8 (CCK-8) assay; flow cytometry was used to detect cell cycle and apoptosis; colony formation assay and JC-1 staining were used to detect cell proliferation and mitochondrial membrane potential changes, respectively. Transcriptome sequencing and western blotting were respectively used to investigate transcription and expression changes in Hep3B cells treated with PMQ. Treatment with 30 and 100 μM PMQ more significantly inhibited cell growth and proliferation in Hep3B cells than in HepG2 and LO2 cells. PMQ induced Hep3B cell cycle arrest and apoptosis by significantly reducing CDK4, CDK6, Cyclin D1, Cyclin E1, Cyclin B1 and Bcl-2 expression and increasing Bax, CDK1 and cleaved PARP levels. Transcriptomic profiles and western blotting results revealed that the MAPK and TNF signaling pathways may be involved in PMQ-induced Hep3B apoptosis.
2024-04-01 | GSE244233 | GEO
Project description:Gene expression profiling was performed by use of serial analysis of gene expression (SAGE) on BJ normal human skin fibroblasts, A-T cells, and BJ and A-T cells transduced with hTERT cDNA and expressing telomerase activity. Keywords = telomere Keywords = telomerase Keywords = TERT Keywords = ataxia telangiectasia mutated Keywords = ATM Keywords = serial analysis of gene expression Keywords = SAGE Keywords = fibroblast Keywords: parallel sample
2004-01-16 | E-GEOD-953 | biostudies-arrayexpress
Project description:Gene expression profiling was performed by use of serial analysis of gene expression (SAGE) on BJ normal human skin fibroblasts, A-T cells, and BJ and A-T cells transduced with hTERT cDNA and expressing telomerase activity. Keywords = telomere Keywords = telomerase Keywords = TERT Keywords = ataxia telangiectasia mutated Keywords = ATM Keywords = serial analysis of gene expression Keywords = SAGE Keywords = fibroblast Keywords: parallel sample
2004-01-17 | GSE953 | GEO
Project description:Differential gene expression in Hep3B and Hep3B SOX4-/- cells
| PRJNA595153 | ENA
Project description:Hotspot mutations in the core promoter region of the telomerase reverse transcriptase (TERT) gene have been well established to associate with aggressive clinical characteristics, radioiodine refractory, tumor recurrence and mortality in thyroid cancer. Several E-twenty-six (ETS) transcription factors were reported to selectively bound to the mutant TERT promoter and activated TERT expression. In this study we aimed to investigate whether TERT promoter mutations confer sensitivity to ETS inhibitor YK-4-279 in thyroid cancer cells and whether this inhibitor could be served as a potential therapeutic agent for thyroid cancer. In vitro assays showed that YK-4-279 treatment sharply suppressed cell viability, colony formation, migration and invasion, as well as induced cell cycle arrest and apoptosis in a panel of thyroid cancer cells. The cell viability after YK-4-279 treatment were similar between cell lines harboring mutant and wild-type TERT promoter. Furthermore, YK-4-279 treatment reduced both luciferase activity and mRNA expression of TERT independent of TERT promoter mutation status. Data from RNA-seq further revealed that YK-4-279 significantly affected biological processes including DNA replication and cell cycle. Reduced DNA helicase activity and decreased expression of several helicase genes were observed after YK-4-279 treatment. Moreover, YK-4-279 significantly inhibited tumor growth and induced apoptosis in a xenograft mice model. Thus, ETS inhibitor YK-4-279 suppressed TERT expression and conferred anti-tumor activity in a TERT promoter mutation-independent manner, and it could be a potential agent for the treatment of advanced thyroid cancers.
2021-04-06 | GSE171473 | GEO