更新于：2024-11-01

IKKγ x ERα

更新于：2024-11-01

基本信息

关联

项与 IKKγ x ERα 相关的药物

Oxabicycloheptene sulfonate(University of Illinois at Urbana-Champaign)

靶点

ERα x IKKγ

作用机制

ERα调节剂 [+1]

在研机构-

原研机构

University of Illinois At UrbanaChampaign

在研适应症-

非在研适应症

子宫内膜异位症

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 IKKγ x ERα 相关的临床结果

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100 项与 IKKγ x ERα 相关的转化医学

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0 项与 IKKγ x ERα 相关的专利（医药）

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项与 IKKγ x ERα 相关的文献（医药）

2024-01-01·Alcohol: Clinical and Experimental Research

The mechanisms underlying alcohol‐induced decreased splenic size: A network meta‐analysis study

Article

作者: Liu, Xiangqian ; Bishir, Muhammed ; Hodgkinson, Colin ; Goldman, David ; Chang, Sulie L

AbstractBackgroundOrgan weight change is widely accepted as a measure of toxicologic pathology. We and other groups have shown that excessive alcohol exposure leads to decreased spleen weight in rodents. This study explores the mechanisms underlying alcohol‐induced splenic injury through a network meta‐analysis.MethodsQIAGEN Ingenuity Pathway Analysis (IPA) and Mammalian Phenotype (MP) Ontology were used to identify alcohol‐related molecules associated with the small spleen phenotype. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and IPA bioinformatics tools were then used to analyze the biologic processes and enriched signaling pathways engaging these molecules. In addition, the “downstream effects analysis” algorithm was used to quantify alcohol's effects.ResultsIPA identified 623 molecules affected by alcohol and a Venn diagram revealed that 26 of these molecules overlapped with those associated with the MP Ontology of small spleen. The 26 molecules are TGFB1, CASP8, MTOR, ESR1, CXCR4, CAMK4, NFKBIA, DRD2, BCL2, FAS, PEBP1, TRAF2, ATM, IGHM, EDNRB, MDM2, GLRA1, PRF1, TLR7, IFNG, ALOX5, FOXO1, IL15, APOE, IKBKG, and RORA. Some of the 26 molecules were also associated with the MP Ontology of abnormal white pulp and red pulp morphology of the spleen, abnormal splenic cell ratio, decreased splenocyte number, abnormal spleen physiology, increased splenocyte apoptosis, and reduced splenocyte proliferation. STRING and IPA “Core Analysis” showed that these molecules were mainly involved in pathways related to cell apoptosis, proliferation, migration, and immune responses. IPA's “Molecular Activity Predictor” tool showed that concurrent effects of activation and inhibition of these molecules led to decreased spleen size by modulating apoptosis, proliferation, and migration of splenocytes.ConclusionsOur network meta‐analysis revealed that excessive alcohol exposure can damage the spleen through a variety of molecular mechanisms, thereby affecting immune function and human health. We found that alcohol‐mediated splenic atrophy is largely mediated by increased apoptosis signaling, migration of cells, and inhibition of splenocyte proliferation.

2020-12-01·Journal of Ovarian Research2区 · 医学

Integrated analysis of gene expression and DNA methylation profiles in ovarian cancer

2区 · 医学

ArticleOA

作者: Gong, Guanghui ; Yuan, Yishu ; Lin, Ting

AbstractBackgroundOvarian cancer is an epithelial malignancy that intrigues people for its poor outcome and lack of efficient treatment, while methylation is an important mechanism that have been recognized in many malignancies. In this study, we attempt to assess abnormally methylated gene markers and pathways in ovarian cancer by integrating three microarray datasets.MethodsThree datasets including expression (GSE26712 and GSE66957) and methylation (GSE81224) datasets were accessed. GEO2R platform was used to detect abnormally methylated-differentially expressed genes. Protein-protein interaction (PPI) networks were built and analysed for hypermethylated and hypermethylated differentially expressed genes using Cytoscape software and Mcode app. GEPIA and cBioPortal platforms were used to validate the expression of the hub genes and the correlation between their mRNA expressions and methylation levels. Kaplan Meier-plotter platform were used to assess the prognostic significance of the hub genes.ResultsSix hundred eighty-one hypomethylated-upregulated genes were detected and involved in Rap1 signaling pathway, biosynthesis of amino acids, endocrine resistance, apoptosis, pathways in cancer. The hub genes were TNF, UBC, SRC, ESR1, CDK1, PECAM1, CXCR4, MUC1, IKBKG. Additionally, 337 hypermethylated-downregulated genes were detected and involved in pathways in cancer, focal adhesion, sphingolipid signaling pathway, EGFR tyrosine kinase inhibitor resistance, cellular senescence. The hub genes were BDNF, CDC42, CD44, PPP2R5C, PTEN, UBB, BMP2, FOXO1, KLHL2. TNF, ESR1, MUC1, CD44, PPP2R5C, PTEN, UBB and FOXO1 showed significant negative correlation between their mRNA expressions and methylation levels. TNF, ESR1 and FOXO1 showed prognostic significance.ConclusionsTwo novel gene networks were found for ovarian cancer. TNF, ESR1, MUC1 and FOXO1 are our candidate genes that might take part in ovarian cancer progression in an epigenetic approach, TNF, ESR1 and FOXO1 may serve as potential markers for ovarian cancer prognosis evaluation.

2017-12-01·Breast Cancer Research and Treatment2区 · 医学

BRCA1-mimetic compound NSC35446.HCl inhibits IKKB expression by reducing estrogen receptor-α occupancy in the IKKB promoter and inhibits NF-κB activity in antiestrogen-resistant human breast cancer cells

2区 · 医学

Article

作者: Nathan, Shyam ; Brown, Milton L ; De Oliveira, Eliseu ; Rosen, Eliot M ; Tomita, York A ; Ma, Yongxian

PURPOSEWe previously identified small molecules that fit into a BRCA1-binding pocket within estrogen receptor-alpha (ERα), mimic the ability of BRCA1 to inhibit ERα activity ("BRCA1-mimetics"), and overcome antiestrogen resistance. One such compound, the hydrochloride salt of NSC35446 ("NSC35446.HCl"), also inhibited the growth of antiestrogen-resistant LCC9 tumor xenografts. The purpose of this study was to investigate the down-stream effects of NSC35446.HCl and its mechanism of action.METHODSHere, we studied antiestrogen-resistant (LCC9, T47DCO, MCF-7/RR, LY2), ERα-negative (MDA-MB-231, HCC1806, MDA-MB-468), and antiestrogen-sensitive (MCF-7) cell lines. Techniques utilized include RNA-seq, qRT-PCR, cell growth analysis, cell-cycle analysis, Western blotting, luciferase reporter assays, TUNEL assays, in silico analysis of the IKKB gene, and ChIP assays.RESULTSSC35446.HCl inhibited proliferation and induced apoptosis in antiestrogen-resistant LCC9, T47DCO, MCF-7/RR, and LY2 cells but not in ERα-negative breast cancer cell lines. IKKB (IKKβ, IKBKB), an upstream activator of NF-κB, was identified as a BRCA1-mimetic-regulated gene based on an RNA-seq analysis. NSC35446.HCl inhibited IKKB, IKKA, and IKKG/NEMO mRNA and protein expression in LCC9 cells. NSC35446.HCl also inhibited NF-κB activity and expression of NF-κB target genes. In silico analysis of the IKKB promoter identified nine estrogen response element (ERE) half-sites and one ERE-like full-site. ChIP assays revealed that ERα was recruited to the ERE-like full-site and five of the nine half-sites and that ERα recruitment was inhibited by NSC35446.HCl in LCC9 and T47DCO cells.CONCLUSIONSThese studies identify functional EREs in the IKKB promoter and identify IKKB as an ERα and NSC35446.HCl-regulated gene, and they suggest that NF-κB and IKKB, which were previously linked to antiestrogen resistance, are targets for NSC35446.HCl in reversing antiestrogen resistance.