Identification of a signal transducer and activator of transcription 3-regulated microRNA-200 family signature with prognostic potential in early gastric cancer
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ABSTRACT:
ORGANISM(S): Mus musculus synthetic construct
PROVIDER: GSE93196 | GEO | 2017/12/01
SECONDARY ACCESSION(S): PRJNA360279
REPOSITORIES: GEO
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Project description:Identification of a signal transducer and activator of transcription 3-regulated microRNA-200 family signature with prognostic potential in early gastric cancer
| PRJNA360279 | ENA
Project description:The excessive and continuous activated Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway leads to the proliferation and migration of malignant cells resulting in the occurrence and development of almost all of cancers. The defined gene sets specifically activated by different STAT proteins are relied on their genomic accessibility by the interplay of certain STAT proteins with other potential cofactors. However, we have no clue about the status of human activated STAT dimers in the nucleus, as well as the intercrossing modules of synergic, supplementary or competitive relationship among each other in colorectal cancer. In current study, chromatin immunoprecipitation sequencing (ChIP-seq) was conducted to explore the genome-scale binding signatures of STAT1, STAT2, STAT3, STAT5A/B and STAT6 in human HCT-116 CRC cells. Moreover, STAT3 binding on genomic DNA was also investigated in HCT116 cells with NR5A2 knockdown.
2021-11-08 | E-MTAB-11113 | biostudies-arrayexpress
Project description:BackgroundSignal transducer and activator of transcription (STAT) is a unique protein family that binds to DNA and plays a vital role in regulating major physiological cellular processes. Seven STAT genes have been identified in the human genome. Several studies suggest STAT family members to be involved in cancer development, progression, and metastasis. However, the predictive relationship between STAT family expression and immune cell infiltration in endometrial cancer remains unknown.MethodsWe explored STAT family expression and prognosis in endometrial cancer using various databases. The STRING, GeneMANIA, and DAVID databases, along with GO and KEGG analyses, were used to construct a protein interaction network of related genes. Finally, the TIMER database and ssGSEA immune infiltration algorithm were used to investigate the correlation of STAT family expression with the immune infiltration level in uterine corpus endometrial carcinoma (UCEC).ResultsOur study showed that different STAT family members are differentially expressed in UCEC. STAT1 and STAT2 expression increased at various stages of UCEC, and STAT5A, STAT5B, and STAT6 levels were decreased. STAT3 and STAT4 expression was not significantly different between UCEC and normal tissues. High STAT1 expression may be a prognostic disadvantage of UCEC, and high STAT6 expression may improve UCEC patient prognosis. The STAT family-associated genes were significantly enriched in signal transduction, protein binding, DNA binding, and ATP binding upon GO analysis. Related genes in the KEGG analysis were mainly enriched in pathways in cancer, viral carcinogenesis, chemokine signaling pathway, JAK/STAT signaling pathway, and regulation of the actin cytoskeleton. In terms of immune infiltration, STAT1 and STAT2 were positively correlated with B, CD8+ T, CD4+ T, and dendritic cells, and neutrophils (p < 0.05). All STAT family members were positively correlated with neutrophils and dendritic cells (p < 0.05). STAT1 and STAT2 showed similar correlations with all immune cell types, whereas STAT1 and STAT6 showed opposite correlations.ConclusionThese findings suggest that the STAT family is a prognostic marker, and the immune infiltration level, a therapeutic target, for endometrial cancer.
| S-EPMC8993664 | biostudies-literature
Project description:Signal transducer and activator of transcription (STAT) family genes-of which there are seven members: STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, and STAT6-have been associated with the progression of multiple cancers. However, their prognostic values in glioma remain unclear. In this study, we systematically investigated the expression, the prognostic value, and the potential mechanism of the STAT family genes in glioma. The expression of STAT1/2/3/5A/6 members were significantly higher and positively correlated with IDH mutations, while the expression of STAT5B was lower and negatively correlated with IDH mutations in glioma. Survival analysis indicated that the upregulation of STAT1/2/3/5A/6 and downregulation of STAT5B expression was associated with poorer overall survival in glioma. Joint effects analysis of STAT1/2/3/5A/5B/6 expression suggested that the prognostic value of the group was more significant than that of each individual gene. Thus, we constructed a risk score model to predict the prognosis of glioma. The receiver operating characteristic curve and calibration curves showed good performance as prognostic indicators in both TCGA (The Cancer Genome Atlas) and the CGGA (Chinese Glioma Genome Atlas) databases. Furthermore, we analyzed the correlation between STAT expression with immune infiltration in glioma. The Protein-protein interaction network and enrichment analysis showed that STAT members and co-expressed genes mainly participated in signal transduction activity, Hepatitis B, the Jak-STAT signaling pathway, transcription factor activity, sequence-specific DNA binding, and the cytokine-mediated signaling pathway in glioma. In summary, our study analyzed the expression, prognostic values, and biological roles of the STAT gene family members in glioma, based on which we developed a new risk score model to predict the prognosis of glioma more precisely.
| S-EPMC8283826 | biostudies-literature
Project description:The aberrantly expressed signal transducer and activator of transcription 3 (STAT3) predicts poor prognosis, primarily in estrogen receptor positive (ER(+)) breast cancers. Activated STAT3 is overexpressed in luminal A subtype cells. The mechanisms contributing to the prognosis and/or subtype relevant features of STAT3 in ER(+) breast cancers are through multiple interacting regulatory pathways, including STAT3-MYC, STAT3-ERα, and STAT3-MYC-ERα interactions, as well as the direct action of activated STAT3. These data predict malignant events, treatment responses and a novel enhancer of tamoxifen resistance. The inferred crosstalk between ERα and STAT3 in regulating their shared target gene-METAP2 is partially validated in the luminal B breast cancer cell line-MCF7. Taken together, we identify a poor prognosis relevant gene set within the STAT3 network and a robust one in a subset of patients. VEGFA, ABL1, LYN, IGF2R and STAT3 are suggested therapeutic targets for further study based upon the degree of differential expression in our model.
| S-EPMC3921136 | biostudies-literature
Project description:STAT4 is a member of the signal transducer and activator of transcription (STAT) family of molecules that localizes to the cytoplasm. STAT4 regulates various genes expression as a transcription factor after it is phosphorylated, dimerizes and translocates to the nucleus. STAT4 activation is detected virtually in the liver of several mouse models of liver injury, as well as the human liver of chronic liver diseases. STAT4 gene polymorphism has been shown to be associated with the antiviral response in chronic hepatitis C and drug-induced liver injury (DILI), primary biliary cirrhosis (PBC), HCV-associated liver fibrosis and in hepatocellular carcinoma (HCC). However, the roles of STAT4 in the pathogeneses of liver diseases are still not understood entirely. This review summarizes the recent advances on the functional roles of STAT4 and its related cytokines in liver diseases, especially in regulating hepatic anti-viral responses, inflammation, proliferation, apoptosis and tumorigenesis. Targeting STAT4 signaling pathway might be a promising strategy in developing therapeutic approaches for treating hepatitis in order to prevent further injury like cirrhosis and liver cancer.
| S-EPMC4366643 | biostudies-literature
Project description:The review summarizes our current knowledge of the role of signal transducer and activator of transcription 3 (STAT3) signaling in skeletal muscle regeneration and the maintenance of muscle mass.STAT3 signaling plays a pivotal role in regulating the function of multiple cell types in skeletal muscle. This includes muscle stem cells, myofibers, and macrophages. It regulates muscle stem cell function by antagonizing self-renewal. STAT3 also functions in myofibers to regulate skeletal muscle mass. This is highly relevant under pathological conditions where STAT3 activation promotes protein degradation and muscle atrophy. Transient pharmacological inhibition of STAT3 partially prevents muscle wasting. However, the mechanisms responsible for the improvement of muscle condition are not currently well understood. This is because of the complexity of the system, as STAT3 has a critical role in regulating the function of several cell types residing in skeletal muscle.Muscle wasting is associated with several human diseases such as muscle dystrophies or cancer cachexia. However, currently there are no effective treatments for this condition, and there is a critical need to identify new potential targets for the development of efficient therapeutic approaches.
| S-EPMC4866604 | biostudies-literature
Project description:Excessive proliferation and stabilization of the microtubule (MT) array in cardiac myocytes can accompany pathological cardiac hypertrophy, but the molecular control of these changes remains poorly characterized. In this study, we examined MT stabilization in two independent murine models of heart failure and revealed increases in the levels of post-translationally modified stable MTs, which were closely associated with STAT3 activation. To explore the molecular signaling events contributing to control of the cardiac MT network, we stimulated cardiac myocytes with an ?-adrenergic agonist phenylephrine (PE), and observed increased tubulin content without changes in detyrosinated (glu-tubulin) stable MTs. In contrast, the hypertrophic interleukin-6 (IL6) family cytokines increased both the glu-tubulin content and glu-MT density. When we examined a role for ERK in regulating cardiac MTs, we showed that the MEK/ERK-inhibitor U0126 increased glu-MT density in either control cardiac myocytes or following exposure to hypertrophic agents. Conversely, expression of an activated MEK1 mutant reduced glu-tubulin levels. Thus, ERK signaling antagonizes stabilization of the cardiac MT array. In contrast, inhibiting either JAK2 with AG490, or STAT3 signaling with Stattic or siRNA knockdown, blocked cytokine-stimulated increases in glu-MT density. Furthermore, the expression of a constitutively active STAT3 mutant triggered increased glu-MT density in the absence of hypertrophic stimulation. Thus, STAT3 activation contributes substantially to cytokine-stimulated glu-MT changes. Taken together, our results highlight the opposing actions of STAT3 and ERK pathways in the regulation of MT changes associated with cardiac myocyte hypertrophy.
| S-EPMC3020766 | biostudies-literature
Project description:Abstract Aberrantly expressed signal transducer and activator of transcription 3 (STAT3) predicts poor prognosis primarily in estrogen receptor positive (ER(+)) breast cancers and activated STAT3 is overexpressed in luminal A subtype cells. The mechanisms contributing to the prognosis and/or subtype relevant features of *STAT3* in ER(+) breast cancers are* *through multiple interacting regulatory pathways including STAT3-MYC, STAT3-ER , STAT3-MYC-ER interactions and the direct action of activated STAT3. These results predict malignant events, treatment responses and a novel enhancer of tamoxifen resistance. The inferred crosstalk between ER and STAT3 in regulating their shared target gene-*METAP2* is partially validated in the luminal B breast cancer cell line-MCF7. Taken together, we identify a poor prognosis relevant gene set within the *STAT3* network and a robust one in a subset of patients. *VEGFA*, *ABL1*, *LYN*, *IGF2R* and* STAT3* are suggested therapeutic targets for further study based upon the degree of differential expression in our model. Keywords: STAT3 transcriptional regulatory network, prognosis, tamoxifen resistance, tumorigenesis, breast cancer.
2010-11-04 | GSE24124 | GEO
Project description:Gastric cancer remains a significant health burden worldwide. In continuation of our previous study and development of effective small molecules against gastric cancer, a series of benzochalcone analogues involving heterocyclic molecules were synthesised and biologically evaluated in vitro and in vivo. Among them, the quinolin-6-yl substituted derivative KL-6 inhibited the growth of gastric cancer cells (HGC27, MKN28, AZ521, AGS, and MKN1) with a submicromolar to micromolar range of IC50, being the most potent one in this series. Additionally, KL-6 significantly inhibited the colony formation, migration and invasion, and effectively induced apoptosis of MKN1 cells in a concentration-dependent manner. The mechanistic study revealed that KL-6 could concentration-dependently suppress STAT3 phosphorylation, which may partly contribute to its anticancer activity. Furthermore, in vivo antitumour study on the MKN1 orthotopic tumour model showed that KL-6 effectively inhibited tumour growth (TGI of 78%) and metastasis without obvious toxicity. Collectively, compound KL-6 may support the further development of candidates for gastric cancer treatment.
| S-EPMC9297716 | biostudies-literature