Effect of HSF1 overexpression in non-tumorigenic human breast epithelial MCF10A cell line
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE241795 | GEO | 2023/11/02
REPOSITORIES: GEO
Similar Datasets
Project description:Thermotolerance is a crucial virulence attribute for Cryptococcus neoformans, which causes fatal fungal meningitis in humans. A protein kinase, Sch9, suppresses the thermotolerance of C. neoformans but its regulatory mechanism remains unknown. Here we elucidated the Sch9-dependent and -independent signaling networks for modulating the thermotolerance of C. neoformans through a genome-wide transcriptome analysis and reverse genetics approaches. We found that more than 1,800 genes were under transcriptional control during temperature upshift. Genes encoding for molecular chaperones and heat shock proteins were mainly upregulated, while those for translation, transcription, and sterol biosynthesis were highly suppressed. In this process Sch9 was found to regulate basal or induced expression levels of some temperature-responsive genes. Interestingly we found that Sch9 was involved in transcriptional regulation of the Ire1 kinase, which is a key sensor for the unfolded protein response pathway, and was found to be involved in ER stress response. Most notably, our data demonstrated that expression of HSF1, encoding a heat shock transcription factor 1, was downregulated during temperature upshift and Sch9 suppresses its downregulation. In spite of such expression patterns, Hsf1 was essential for growth and its overexpression indeed promoted the thermotolerance of C. neoformans, suggesting dual roles of Hsf1 in thermotolerance. This idea was supported by additional transcriptome analysis with HSF1 overexpression strain, which revealed that Hsf1 served as both activator and repressor. Hsf1 promoted genes such as Hsp104 and Hsp70 (Ssa1 and Ssa2), both of which were found to be highly upregulated during temperature upshift and required for thermotolerance, while Hsf1 repressed genes involved in oxidative stress and thermotolerance.
2015-06-01 | GSE66508 | GEO
Project description:Thermotolerance is a crucial virulence attribute for Cryptococcus neoformans, which causes fatal fungal meningitis in humans. A protein kinase, Sch9, suppresses the thermotolerance of C. neoformans but its regulatory mechanism remains unknown. Here we elucidated the Sch9-dependent and -independent signaling networks for modulating the thermotolerance of C. neoformans through a genome-wide transcriptome analysis and reverse genetics approaches. We found that more than 1,800 genes were under transcriptional control during temperature upshift. Genes encoding for molecular chaperones and heat shock proteins were mainly upregulated, while those for translation, transcription, and sterol biosynthesis were highly suppressed. In this process Sch9 was found to regulate basal or induced expression levels of some temperature-responsive genes. Interestingly we found that Sch9 was involved in transcriptional regulation of the Ire1 kinase, which is a key sensor for the unfolded protein response pathway, and was found to be involved in ER stress response. Most notably, our data demonstrated that expression of HSF1, encoding a heat shock transcription factor 1, was downregulated during temperature upshift and Sch9 suppresses its downregulation. In spite of such expression patterns, Hsf1 was essential for growth and its overexpression indeed promoted the thermotolerance of C. neoformans, suggesting dual roles of Hsf1 in thermotolerance. This idea was supported by additional transcriptome analysis with HSF1 overexpression strain, which revealed that Hsf1 served as both activator and repressor. Hsf1 promoted genes such as Hsp104 and Hsp70 (Ssa1 and Ssa2), both of which were found to be highly upregulated during temperature upshift and required for thermotolerance, while Hsf1 repressed genes involved in oxidative stress and thermotolerance.
2015-06-01 | GSE66509 | GEO
Project description:Transgelin was the top-ranked marker of metastatic potential identified in the comparison of node-positive colorectal cancer (CRC) versus node-negative CRC in our previous study. Transgelin is localized in the nucleus of cultured CRC cells and microRNA-mediated knockdown of TAGLN (the gene encoding transgelin) expression modulates the expression of genes involved in the epithelial-to-mesenchymal transition. We performed gene expression profiling on control and transgelin-overexpressing RKO cells using Affymetrix microarray technology. The plasmid carrying TAGLN was generated using the pcDNA6.2/EmGFP-Bsd/V5-DEST vector (Invitrogen, Carlsbad, CA) and the pDONR221-TAGLN-mut plasmid from a previous study by an LR recombination reaction (http://www.invitrogen.com). After lipofectamine-mediated transfection of the TAGLN-carrying plasmid or the vector-only control plasmid, stable transfectants were selected and cultured in medium containing 25 μg/ml blasticidin followed by RNA extraction and hybridization on Affymetrix microarrays. Six samples were obtained from three independent experiments (technical replicates).
2013-07-18 | E-GEOD-48998 | biostudies-arrayexpress
Project description:Tuberous sclerosis complex (TSC) is a rare genetic disease caused by abnormal of TSC1 or TSC2 gene. Our previous data deduced that IQGAP2 can be one of the genes potentially responsible for non-TSC1 or TSC2 mutation TSC patients. To investigate the pathogenesis of IQGAP2 in TSC, we performed global transcriptome, proteome, and phosphoproteome analyses and found the alter of genes related to mTOR signaling pathway in IQGAP2 knockdown cells. In addition, we found that knockdown of IQGAP2 resulted in increased cell proliferation and enhanced the phosphorylation level of AKT and S6K by functional analysis, meanwhile, the AKT and mTOR inhibitors can partially rescue cell abnormal proliferation by decreasing hyperphosphorylation. Our data revealed a potential connection between mTOR signaling pathway and aberrant cell proliferation in IQGAP2 knockdown cells, and provide a new latent therapeutic strategy for non-TSC1 or TSC2 mutation patients.
2022-09-22 | GSE213715 | GEO
Project description:Whole body knockout mice lacking IQ-motif containing GTPase-activating protein 2 (IQGAP2) develop spontaneous hepatocellular carcinoma (HCC) at the age of 12 months and older (Schmidt et al., 2008). Hepatic transcript expression profiles were obtained for IQGAP2 knockout and wild-type control mice of two age groups, 6- and 24-month-old. Liver samples from 24-month-old IQGAP2 knockout mice were HCC tumors, livers from all other groups were tumor-free. Results provide insights into the potential role of IQGAP2 as a liver-specific tumor suppressor. Transcript profiles of four groups of mouse livers (N = 3 in each group) were compared using Affymetrix GeneChip® Mouse Genome 430 2.0 Array. The groups included livers from 6- and 24-month-old wild-type (WT) mice and 6- and 24-month-old (KO) Iqgap2-/- mice.
2013-12-13 | E-GEOD-46646 | biostudies-arrayexpress
Project description:Whole body knockout mice lacking IQ-motif containing GTPase-activating protein 2 (IQGAP2) develop spontaneous hepatocellular carcinoma (HCC) at the age of 12 months and older (Schmidt et al., 2008). Hepatic transcript expression profiles were obtained for IQGAP2 knockout and wild-type control mice of two age groups, 6- and 24-month-old. Liver samples from 24-month-old IQGAP2 knockout mice were HCC tumors, livers from all other groups were tumor-free. Results provide insights into the potential role of IQGAP2 as a liver-specific tumor suppressor.
2013-12-13 | GSE46646 | GEO
Project description:Failure of the nucleus pulposus (NP) causes intervertebral disc (IVD) disease and associated low-back pain, which are highly prevalent among the aged populations. Molecular and cellular changes underpinning the structural failures in age-associated IVD diseases (IDDs) remain poorly elucidated. Here, we first identified that TAGLN, which encodes the cytoskeleton regulator transgelin, was transcribed in healthy NPs of both human and mouse, but diminished with ageing. Immunostaining showed that TAGLN were expressed on the peripheral of mouse NP (periNP). Lineage analyses in Tagln-CreERT2 mice showed that NP cells were derived from Tagln+ cells in the periNP. The PeriNP cells were proliferative and can differentiate into the inner NP (innerNP). These Tagln+ cells and their descendants diminish with ageing or puncture-induced degeneration. Single-cell transcriptomics from neonatal and adult Tagln-CreERT2 IVDs confirmed that Tagln descendants uniquely populate the NP, wherein four sub-populations were identified: chondrocyte-like, Cd228+, Tagln+ and Car3+. Immunostaining confirmed Car3 expressed in innerNP. Computational analysis indicated the lineage trajectory from Tagln+ to Car3+ sub-population, along with the involvement of Fos/Jun/TGFβ cascades and partial epithelial-to-mesenchymal transition process. Removal of TGFβ mediator Smad4 by notochord specific Foxa2mNE-Cre resulted in decreased Tagln+ cells and abnormal disc morphology, resembling disc degeneration. Our study generates a single-cell transcriptomic atlas for healthy IVD, identifies Tagln+ PeriNP cells as a progenitor pool crucial for the IVD homeostasis, and provides potential targets for regenerative cell therapy against IVD degeneration.
2024-05-14 | GSE201396 | GEO
Project description:The tumor microenvironment (TME) comprises numerous forms of cellular stress, which can activate Heat Shock Factor 1 (HSF1), the master transcription factor of the proteotoxic stress response. We profiled HSF1 activity across tumor-infiltrating immune populations, revealing the highest activity in CD8+ T cells and the lowest in natural killer (NK) cells. To elucidate the mechanisms through which HSF1 regulates immune surveillance, we generated an in vivo model of augmented HSF1 activity. Tumor challenge revealed that accumulation of HSF1 dampens NK-mediated tumor immunity and impairs both cytotoxicity and production of interferon gamma (IFN-γ) in NK cells. Single-cell transcriptional profiling identified a loss of anti-tumor signaling pathways, including interferon signaling, within the HSF1-enhanced TME. In NK cells, integration of chromatin accessibility with transcriptomics revealed that HSF1 deregulates accessibility and expression of genes encoding for NK receptors, leading to an inhibitory bias.
2021-02-26 | GSE167550 | GEO
Project description:The tumor microenvironment (TME) comprises numerous forms of cellular stress, which can activate Heat Shock Factor 1 (HSF1), the master transcription factor of the proteotoxic stress response. We profiled HSF1 activity across tumor-infiltrating immune populations, revealing the highest activity in CD8+ T cells and the lowest in natural killer (NK) cells. To elucidate the mechanisms through which HSF1 regulates immune surveillance, we generated an in vivo model of augmented HSF1 activity. Tumor challenge revealed that accumulation of HSF1 dampens NK-mediated tumor immunity and impairs both cytotoxicity and production of interferon gamma (IFN-γ) in NK cells. Single-cell transcriptional profiling identified a loss of anti-tumor signaling pathways, including interferon signaling, within the HSF1-enhanced TME. In NK cells, integration of chromatin accessibility with transcriptomics revealed that HSF1 deregulates accessibility and expression of genes encoding for NK receptors, leading to an inhibitory bias.
2021-02-26 | GSE167549 | GEO
Project description:The tumor microenvironment (TME) comprises numerous forms of cellular stress, which can activate Heat Shock Factor 1 (HSF1), the master transcription factor of the proteotoxic stress response. We profiled HSF1 activity across tumor-infiltrating immune populations, revealing the highest activity in CD8+ T cells and the lowest in natural killer (NK) cells. To elucidate the mechanisms through which HSF1 regulates immune surveillance, we generated an in vivo model of augmented HSF1 activity. Tumor challenge revealed that accumulation of HSF1 dampens NK-mediated tumor immunity and impairs both cytotoxicity and production of interferon gamma (IFN-γ) in NK cells. Single-cell transcriptional profiling identified a loss of anti-tumor signaling pathways, including interferon signaling, within the HSF1-enhanced TME. In NK cells, integration of chromatin accessibility with transcriptomics revealed that HSF1 deregulates accessibility and expression of genes encoding for NK receptors, leading to an inhibitory bias.
2021-02-26 | GSE167551 | GEO