HCSGD entry for STAT3
1. General information
| Official gene symbol | STAT3 |
|---|---|
| Entrez ID | 6774 |
| Gene full name | signal transducer and activator of transcription 3 (acute-phase response factor) |
| Other gene symbols | APRF HIES |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0000122 | Negative regulation of transcription from RNA polymerase II promoter | TAS | biological_process |
| GO:0000981 | Sequence-specific DNA binding RNA polymerase II transcription factor activity | IEA | molecular_function |
| GO:0001103 | RNA polymerase II repressing transcription factor binding | IPI | molecular_function |
| GO:0001659 | Temperature homeostasis | IEA ISS | biological_process |
| GO:0001754 | Eye photoreceptor cell differentiation | IEA ISS | biological_process |
| GO:0003677 | DNA binding | IEA ISS | molecular_function |
| GO:0003700 | Sequence-specific DNA binding transcription factor activity | IEA TAS | molecular_function |
| GO:0004871 | Signal transducer activity | IEA | molecular_function |
| GO:0004879 | Ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity | IDA | molecular_function |
| GO:0005509 | Calcium ion binding | IEA | molecular_function |
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005634 | Nucleus | IDA IEA ISS | cellular_component |
| GO:0005654 | Nucleoplasm | TAS | cellular_component |
| GO:0005730 | Nucleolus | IDA | cellular_component |
| GO:0005737 | Cytoplasm | IDA IEA ISS | cellular_component |
| GO:0005829 | Cytosol | TAS | cellular_component |
| GO:0005886 | Plasma membrane | IEA ISS | cellular_component |
| GO:0006351 | Transcription, DNA-templated | IEA | biological_process |
| GO:0006355 | Regulation of transcription, DNA-templated | IDA | biological_process |
| GO:0006357 | Regulation of transcription from RNA polymerase II promoter | ISS | biological_process |
| GO:0006606 | Protein import into nucleus | IDA | biological_process |
| GO:0006928 | Cellular component movement | TAS | biological_process |
| GO:0006953 | Acute-phase response | IEA | biological_process |
| GO:0007165 | Signal transduction | TAS | biological_process |
| GO:0007259 | JAK-STAT cascade | TAS | biological_process |
| GO:0007399 | Nervous system development | TAS | biological_process |
| GO:0008134 | Transcription factor binding | IEA IPI | molecular_function |
| GO:0008283 | Cell proliferation | IEA | biological_process |
| GO:0016032 | Viral process | IEA | biological_process |
| GO:0016310 | Phosphorylation | IEA ISS | biological_process |
| GO:0019221 | Cytokine-mediated signaling pathway | NAS | biological_process |
| GO:0019827 | Stem cell maintenance | IEA | biological_process |
| GO:0019901 | Protein kinase binding | IEA ISS | molecular_function |
| GO:0019903 | Protein phosphatase binding | IPI | molecular_function |
| GO:0019953 | Sexual reproduction | IEA ISS | biological_process |
| GO:0030522 | Intracellular receptor signaling pathway | IDA | biological_process |
| GO:0031730 | CCR5 chemokine receptor binding | IEA | molecular_function |
| GO:0032355 | Response to estradiol | IDA IEA | biological_process |
| GO:0032870 | Cellular response to hormone stimulus | IDA | biological_process |
| GO:0034097 | Response to cytokine | IEA | biological_process |
| GO:0035259 | Glucocorticoid receptor binding | IEA | molecular_function |
| GO:0040014 | Regulation of multicellular organism growth | IEA | biological_process |
| GO:0042493 | Response to drug | IEA | biological_process |
| GO:0042593 | Glucose homeostasis | IEA ISS | biological_process |
| GO:0042755 | Eating behavior | IEA ISS | biological_process |
| GO:0043565 | Sequence-specific DNA binding | IEA | molecular_function |
| GO:0044212 | Transcription regulatory region DNA binding | IDA | molecular_function |
| GO:0045471 | Response to ethanol | IEA | biological_process |
| GO:0045747 | Positive regulation of Notch signaling pathway | IEA ISS | biological_process |
| GO:0045893 | Positive regulation of transcription, DNA-templated | ISS | biological_process |
| GO:0045944 | Positive regulation of transcription from RNA polymerase II promoter | IDA IEA | biological_process |
| GO:0046983 | Protein dimerization activity | IEA ISS | molecular_function |
| GO:0048011 | Neurotrophin TRK receptor signaling pathway | TAS | biological_process |
| GO:0048708 | Astrocyte differentiation | IEA ISS | biological_process |
| GO:0060019 | Radial glial cell differentiation | IEA ISS | biological_process |
| GO:0060396 | Growth hormone receptor signaling pathway | IDA | biological_process |
| GO:0060397 | JAK-STAT cascade involved in growth hormone signaling pathway | IDA IEA ISS TAS | biological_process |
| GO:0060548 | Negative regulation of cell death | IEA | biological_process |
| GO:0070102 | Interleukin-6-mediated signaling pathway | IDA | biological_process |
| GO:2001223 | Negative regulation of neuron migration | IEA | biological_process |
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4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.0817542913 | 0.8314472664 | 0.6029793500 | 1.0000000000 |
- Individual experiment result
( "-" represent NA in the specific microarray platform )
( "-" represent NA in the specific microarray platform )
| Data source | Up or down | Log fold change |
|---|---|---|
| GSE11954 | Up | 0.0528406677 |
| GSE13712_SHEAR | Up | 0.0759701325 |
| GSE13712_STATIC | Up | 0.0786132155 |
| GSE19018 | Down | -0.0592988955 |
| GSE19899_A1 | Up | 0.1163583381 |
| GSE19899_A2 | Up | 0.1292328678 |
| PubMed_21979375_A1 | Down | -0.7910777719 |
| PubMed_21979375_A2 | Up | 0.3165842833 |
| GSE35957 | Down | -0.0886274403 |
| GSE36640 | Up | 0.3800681626 |
| GSE54402 | Down | -0.1298304078 |
| GSE9593 | Up | 0.1392946138 |
| GSE43922 | Up | 0.2106570280 |
| GSE24585 | Up | 0.5763975658 |
| GSE37065 | Down | -0.0197182067 |
| GSE28863_A1 | Up | 0.6276128370 |
| GSE28863_A2 | Up | 0.5362879803 |
| GSE28863_A3 | Down | -0.5111613564 |
| GSE28863_A4 | Down | -0.0278876980 |
| GSE48662 | Up | 0.2955230286 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
Not regulated by compounds
- Drugs
Not regulated by drugs
- MicroRNAs
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-20b-5p | MIMAT0001413 | MIRT000497 | qRT-PCR//ELISA//ChIP//Western blot | Functional MTI | 20232316 |
| hsa-miR-125b-5p | MIMAT0000423 | MIRT005006 | Microarray | Functional MTI (Weak) | 17891175 |
| hsa-miR-337-3p | MIMAT0000754 | MIRT006959 | Luciferase reporter assay//qRT-PCR//Western blot | Functional MTI | 22723956 |
| hsa-miR-155-5p | MIMAT0000646 | MIRT021003 | Proteomics | Functional MTI (Weak) | 18668040 |
| hsa-miR-93-5p | MIMAT0000093 | MIRT028178 | Sequencing | Functional MTI (Weak) | 20371350 |
| hsa-miR-21-5p | MIMAT0000076 | MIRT031079 | Western blot;Other | Functional MTI | 20048743 |
| hsa-miR-21-5p | MIMAT0000076 | MIRT031079 | Microarray | Functional MTI (Weak) | 18591254 |
| hsa-miR-92a-3p | MIMAT0000092 | MIRT049359 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-miR-20a-5p | MIMAT0000075 | MIRT050559 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-let-7e-5p | MIMAT0000066 | MIRT051593 | CLASH | Functional MTI (Weak) | 23622248 |
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- mirRecord
MicroRNA name | mirBase ID | Target site number | MiRNA mature ID | Test method inter | MiRNA regulation site | Reporter target site | Pubmed ID |
|---|---|---|---|---|---|---|---|
| hsa-miR-21-5p | MIMAT0000076 | 1 | hsa-miR-21 | {Western blot} | {overexpression by miRNA precursor transfection} | 21381024 |
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6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 25 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 26477312 | In addition to the activation of oncogenes c-MYC and STAT3 in tumor cells, a number of cytokines and growth factors, such as IL1beta, IL6 and SPP1 (osteopontin, a key biomarker for PCa), were upregulated in NFATc1-induced PCa, establishing a tumorigenic microenvironment involving both NFATc1 positive and negative cells for prostate tumorigenesis |
| 26085373 | Mechanistically, we show that Pten loss increases CK2 levels by activating STAT3 |
| 25847123 | SirT1 and STAT3 protect retinal pigmented epithelium cells against oxidative stress |
| 25847123 | It has been previously demonstrated that there are interactions between sirtuin 1 (SirT1) and signal transducer and activator of transcription 3 (STAT3), which have versatile roles in various microenvironments |
| 25847123 | The present study aimed to investigate the interactions between SirT1 and STAT3 in RPEs, following exposure to oxidative stress |
| 25847123 | The results revealed a downregulation of SirT1 expression, and an upregulation of STAT3 expression during oxidative stress |
| 25847123 | Furthermore, gain- and loss-of-function experiments indicated that SirT1 had negative effects on the regulation of STAT3 expression in RPEs during oxidative stress |
| 25847123 | Notably, STAT3 directly protected the cells from oxidative stress, rather than depending on SirT1 |
| 25847123 | Additionally, the protective effects of STAT3 had no association with the modulation of cell senescence during oxidative stress |
| 25847123 | In conclusion, SirT1 had negative effects on the regulation of STAT3 expression during oxidative stress |
| 25847123 | However, SirT1 and STAT3 demonstrated protective roles against oxidative stress in RPEs |
| 25419563 | In addition, we identified IL-6, a known pleiotropic cytokine, as a principal mediator for the tumor-promoting activity of s-UCMSCs by induction of STAT3 phosphorylation |
| 25412315 | BIS targeting induces cellular senescence through the regulation of 14-3-3 zeta/STAT3/SKP2/p27 in glioblastoma cells |
| 25412315 | As an underlying molecular mechanism, we demonstrate that the loss of activity of signal transducer and activator of transcription 3 (STAT3) was specifically linked to the suppression of SKP2 expression |
| 25412315 | Despite a reduction in phospho-STAT3 levels, total STAT3 levels were unexpectedly increased by BIS depletion, specifically in the insoluble fraction |
| 25412315 | In addition, the ectopic expression of 14-3-3zeta blocked senescence caused by BIS depletion, which was paralleled with a decrease in insoluble STAT3 in A172 glioblastoma cells |
| 25412315 | Therefore, our findings suggest that a downregulation of BIS expression could serve as a potential strategy for restricting tumor progression via an induction of senescence through the regulation of STAT3/SKP2/p27 pathway |
| 24416650 | In this review, we describe recent advances in studies on the roles of IL-6 and its downstream signal transducer and activator of transcription 3 (STAT3) in regulating premature cellular senescence |
| 24416650 | We describe how cytokines regulate the process of senescence by activating STAT3 in one system and anti-senescence or tumorigenesis in other systems |
| 24400224 | Recent studies have elucidated roles for NF-kappaB, STAT3 and JNK as possible missing links |
| 24272483 | Mechanistically, depletion or pharmacologic inhibition of CypB caused hyperactivation of the oncogenic RAS-mitogen-activated protein kinase pathway, induction of cellular senescence signals, and death resulting from loss of MYC, mutant p53, Chk1, and Janus-activated kinase/STAT3 signaling |
| 23984931 | STAT1 and STAT3 activity were increased in tBHP-induced cells |
| 23953057 | Although it is reported that interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) is activated by human papillomavirus (HPV) infection in cervical cancer cells, little is known about the role of IL-6/STAT3 in tumour microenvironment during development of the disease |
| 23953057 | In this study, we found that cancer-associated fibroblasts (CAF) but not normal fibroblasts (NF) secrete high level of IL-6 with activated STAT3 and appear senescent at early passages in culture or in cervical cancer tissues infected with high-risk HPV, and that treatment of NF with recombinant IL-6 or CAF conditioned medium (CM) induces activation of STAT3 and cellular senescence |
| 23953057 | IL-6 and STAT3 are either upregulated or activated in Siha and Hela cells infected with HPV 16 or 18, but not in C33A and ME180 cells without HPV 16 or 18 infection |
| 23953057 | Overexpression of HPV early proteins 6 (E6) activates STAT3, increases IL-6 expression and tumour burden in C33A and ME180 cells, while silencing of HPV E6 by specific shRNA reduces STAT3 activation, IL-6 expression, and tumour formation in Siha and HeLa cells, so does silencing of STAT3 by specific shRNA in HeLa and C33A/E6 cells |
| 23953057 | The tumour growth of cervical cancer cells reconstituted with CAF or NF is largely affected by inhibition of fibroblast senescence with STAT3 inhibitor or with IL-6 antibody treatment |
| 23897841 | Instead, the prompt inhibition of Janus kinase 2 (Jak2), tyrosine kinase 2 (Tyk2), and signal transducer and activator of transcription 3 (Stat3) activation was observed in cells undergoing senescence |
| 23897841 | Expression of constitutively activated Stat3 or human telomerase reverse transcriptase (hTERT), as well as knockdown of Shp2f, efficiently counteracted GADD45G-induced senescence |
| 23599344 | In human prostate neoplasms, high levels of phosphorylated ERK were found in benign lesions, correlating with other senescence markers and low levels of STAT3, one of the SAPD targets |
| 23178160 | Progestin drives breast cancer growth by inducing p21(CIP1) expression through the assembly of a transcriptional complex among Stat3, progesterone receptor and ErbB-2 |
| 23178160 | We found that the synthetic progestin medroxyprogesterone acetate (MPA) upregulates p21(CIP1) protein expression via c-Src, signal transducer and activator of transcription 3 (Stat3) and ErbB-2 phosphorylation |
| 23178160 | Interestingly, we determined that progestin drives p21(CIP1) transcriptional activation via a novel nonclassical transcriptional mechanism in which progesterone receptor is recruited along with Stat3 and ErbB-2 to a Stat3 binding site at p21(CIP1) promoter |
| 23178160 | Our findings revealed that ErbB-2 functions as a coactivator of Stat3 in progestin induction of p21(CIP1) transcriptional activation |
| 23178160 | Moreover, we provided evidence that Stat3 and nuclear ErbB-2 are key players in progestin-induced p21(CIP1) regulation |
| 22889746 | Stat3 contributes to indoxyl sulfate-induced inflammatory and fibrotic gene expression and cellular senescence |
| 22889746 | BACKGROUND/AIM: Increased phosphorylation (activation) of signal transducer and activator of transcription 3 (Stat3) on tyrosine 705 leads to renal fibrosis |
| 22889746 | The present study aimed to determine whether Stat3 is involved in indoxyl sulfate-induced dysfunction of proximal tubular cells |
| 22889746 | METHODS: Localization of phosphorylated Stat3 in the kidneys of normal, subtotally nephrectomized, and AST-120-treated subtotally nephrectomized rats was examined by immunohistochemistry |
| 22889746 | The effect of indoxyl sulfate on phosphorylation of Stat3 and the role of Stat3 on indoxyl sulfate-induced cellular effects were examined using human proximal tubular cells (HK-2 cells) |
| 22889746 | RESULTS: Subtotally nephrectomized rats showed increased immunostaining of phosphorylated Stat3 in the renal tubules compared with normal rats |
| 22889746 | Administration of AST-120, which reduces serum level of indoxyl sulfate, to subtotally nephrectomized rats reduced the immunostaining of phosphorylated Stat3 in the renal tubules |
| 22889746 | Indoxyl sulfate induced phosphorylation of Stat3 in HK-2 cells |
| 22889746 | Stat3 small interfering RNA suppressed indoxyl sulfate-induced expression of an inflammation marker gene (monocyte chemotactic protein-1), fibrosis marker genes (TGF-beta(1), alpha-smooth muscle actin) and a subunit of nuclear factor-kB (p65), and attenuated a cellular senescence marker, senescence-associated beta-galactosidase activity |
| 22889746 | CONCLUSIONS: Stat3 is involved in indoxyl sulfate-induced inflammatory and fibrotic gene expression and cellular senescence in proximal tubular cells |
| 22864395 | Significantly, higher IFNbeta and chemokine gene transcripts have been observed, together with increased STAT1 and decreased STAT3 and NF-kappaB signaling activities |
| 22753933 | Targeting Stat3 induces senescence in tumor cells and elicits prophylactic and therapeutic immune responses against breast cancer growth mediated by NK cells and CD4+ T cells |
| 22753933 | Aberrant Stat3 activation and signaling contribute to malignant transformation by promoting cell cycle progression, inhibiting apoptosis, and mediating tumor immune evasion |
| 22753933 | Stat3 inhibition in tumor cells induces the expression of chemokines and proinflammatory cytokines, so we proposed to apply Stat3-inhibited breast cancer cells as a source of immunogens to induce an antitumor immune response |
| 22753933 | Studies were performed in two murine breast cancer models in which Stat3 is activated: progestin-dependent C4HD cells and 4T1 cells |
| 22753933 | We immunized BALB/c mice with irradiated cancer cells previously transfected with a dominant-negative Stat3 vector (Stat3Y705F) in either a prophylactic or a therapeutic manner |
| 22753933 | Furthermore, inhibition of Stat3 activation in breast cancer cells induced cellular senescence, contributing to their immunogenic phenotype |
| 22753933 | In this work, we provide preclinical proof of concept that ablating Stat3 signaling in breast cancer cells results in an effective immunotherapy against breast cancer growth and metastasis |
| 22753933 | Moreover, our findings showing that Stat3 inactivation results in induction of a cellular senescence program disclose a potential mechanism for immunotherapy research |
| 22473749 | Deletion of STAT3 prevented IL-22-induced HSC senescence in vitro, whereas the overexpression of a constitutively activated form of STAT3 promoted HSC senescence through p53- and p21-dependent pathways |
| 22374671 | Here we demonstrate that IL6 and the soluble IL6 receptor (sIL6R) induce premature senescence in normal human fibroblasts by establishing a senescence-inducing circuit involving the signal transducer and activator of transcription 3 (STAT3) and insulin-like growth factor-binding protein 5 (IGFBP5) |
| 22374671 | We found that STAT3 was required for the events leading to senescence, including the initial early-phase ROS increase and the induction of IL1alpha/beta, IL6 and CXCL8 mRNAs 4-5 d after IL6/sIL6R stimulation, suggesting that STAT3's role is indirect |
| 22253608 | Cytoplasmic polyadenylation element binding protein deficiency stimulates PTEN and Stat3 mRNA translation and induces hepatic insulin resistance |
| 22253608 | An investigation of Cpeb1 knockout mice revealed that the expression of two particular negative regulators of insulin action, PTEN and Stat3, were aberrantly increased |
| 22253608 | Analysis of HepG2 cells, a human liver cell line, depleted of CPEB demonstrated that this protein directly regulates the translation of PTEN and Stat3 mRNAs |
| 22193460 | The STAT1 and STAT3 activity and the expression of p53 and p21(Cip1) were increased after Angiotensin II and H(2)O(2) treatment |
| 21934682 | Profiling the established molecular targets of SHP2 (ERK1/2 and STAT3) confirmed specificity of these siRNAs |
| 21472252 | Compared to the AngII-induced group, in the cells treated with losartan and AG490, the characteristics of cell senescence were ameliorated, and the expression of STAT1, STAT3, pSTAT1 and pSTAT3 was decreased |
| 17761140 | The sphere cells showed stem-like properties with the ability to self-renew, and expressed the stem cell-related STAT3 and Bmi1 genes |
| 16834928 | And supershift assay showed that the sis-inducing factor (SIF) band contained STAT3 proteins |
| 16834928 | STAT3 antisense oligonucleotides could inhibit both Ang II-induced STAT3-DNA binding activity as well as TIMP-1 expression |
| 12812653 | OBJECTIVE: To investigate the changes of STAT3 in cell replicative senescence and the effects of angiotensin II (AngII) on STAT3 |
| 12812653 | Electrophoretic mobility shift assay and Western blotting assay were used to detect the activation of STAT3 during cell replicative senescence and examine the process of STAT3 activation with AngII |
| 12812653 | RESULTS: The synthesis of STAT3 protein during the course of cell replicative senescent increased, the nuclear translocation of phosphorylated STAT3 decreased, and the activities of STAT3 binding DNA reduced |
| 12812653 | AngII induces the activity of STAT3 in replicative senescence WI-38 |
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