Background
Materials and methods
Cell lines and cell culture
Cell viability assay
Cell transfection
Cell apoptosis analysis
Cell migration and invasion assay
Western blot analysis
Human tissue samples and IHC analysis
Dataset and bioinformatics analysis
Computational modeling the molecular signaling network
Statistical analysis
Results
GO and KEGG analysis revealed that ERs affected some membrane receptor signaling pathways
Category | Term | Count | p value | Genes (partial) | |
---|---|---|---|---|---|
Upgrade | BP | Signal transduction | 69 | 1.3E−04 | DLC1, GNA14, CLDN3, WISP2, CDKL2, TNFRSF10C, CCR6, C3, KIT, GPRC5A, CCL20, CD4, ITK |
BP | Immune response | 60 | 7.8E−19 | CHIA, SUSD2, HLA-DMA, CXCR5, SPN, NCR3, TNFRSF10C, CCR2, C3, CXCL2, CCL20, CD4 | |
BP | Cell adhesion | 49 | 1.1E−10 | CXCR3, WISP2, ICAM1, NCAM2, ITGAL, VCAM1, COMP, CD2, THBS4, DPT, TNXB, CASS4 | |
CC | Integral component of membrane | 262 | 2.5E−10 | CCR5, ROR1, MST1R, CYP1B1, ICM1, MMP13, CD22, ABCA3, MUC1, VCAM1 | |
CC | Plasma membrane | 255 | 5.7E−21 | CADM3, AQP1, BTK, ADAM8, ROS1, PIK3CG, CDHR4, CCR5, RAB17, KDR, ICAM1, C3, CD4, MRC1 | |
CC | Extracellular exosome | 182 | 9.3E−16 | PDGFD, MUC1, BMP3, WISP2, ICAM1, AGT, FGG, C3, CD4, CPM | |
MF | Calcium ion binding | 41 | 4.1E−03 | MMP28, FAT4, COMP, ADAM8, CAPN9, CDHR4, PCDHAC1 | |
MF | Protein homodimerization activity | 37 | 3.6E−02 | CADM3, PTGS2, KIT, CD2, CEACAM5, MUC13, FLT3, S100B, CCR2, AOC3 | |
MF | Receptor binding | 30 | 3.4E−05 | CADM3, C3, BLK, BTK, PGR, FGA, RSRO3, TNFSF8, CCL13 | |
KEGG | Cell adhesion molecules (CAMs) | 33 | 9.8E−15 | ITGAL, CADM3, CLDN9, ITGB2, HLA-DMA, ITGAM, VCAM1, CD2, SELPLG, SPN, ICAM1, PTPRC | |
KEGG | Cytokine-cytokine receptor interaction | 29 | 3.1E−06 | GDF5, CXCL2, IL21R, CXCR5, LTB, CSF1R, TNFRSF17, TNFSF8, CCR7, CCL13, CCR6, CD40LG | |
KEGG | Hematopoietic cell lineage | 28 | 2.1E−16 | HLA-DRB1, FCER2, KIT, ITGB3, ITGAM, MS4A1, CD4, CSF3R, CR1, FLT3, CD1A | |
Downgrade | BP | Positive regulation of transcription from RNA polymerase II promoter | 37 | 1.9E−03 | FGFR2, WNT3A, E2F7, SOX2, TP63, JAG1, BARX1, NRG1, DMRT1, CHP2, SIX2, GAL, HMGA2, ITGA6, BMP7 |
BP | Negative regulation of transcription from RNA polymerase II promoter | 26 | 1.7E−02 | FGFR2, E2F7, SOX2, MAGEA1, TP63, NRARP, TRIM29, DMRT1, VAX1, HMGA2, NR0B1, DLX1, FOXE1, TBX18 | |
BP | Oxidation–reduction process | 25 | 3.1E−03 | CYP26A1, OSGIN1, ADH7, ALDH3A1, SESN3, FMO6P, CYP4F3, NOS2, AKR1C1 | |
CC | Extracellular exosome | 84 | 2.6E−03 | WNT3A, RASSF9, SERPINB5, PI3, CNTN1, RAB3B, UGT1A6, KRT5, TGM1, LGALS7, DSC1, IGFBP2, PSAT1 | |
CC | Extracellular region | 55 | 1.2E−03 | WNT3A, JAG1, NRCAM, NRG1, CLCA2, TMPRSS11A, FGFR2, ADH7, FBN2, WNT2B, SOST, BMP7, IGFBP2 | |
CC | Extracellular space | 52 | 9.9E−05 | WNT3A, FGF12, NRG1, MMP10, SERPINB5, FGFBP1, LGALS7, KRT31, WNT2B, SOST, IGFL1, BMP7, IGFBP2 | |
MF | Structural molecule activity | 32 | 7.7E−15 | JAG1, KRT5, CLDN20, SPRR1A, KRT16, SPRR3, CSTA, ADD2 | |
MF | Calcium ion binding | 31 | 8.6E−04 | NELL1, JAG1, NECAB2, CDH8, ANXA8, RPTN, FAT2, TGM3, FBN2, S100A2, CDHR1, CABYR, MMP10, DSC1 | |
MF | Transcription factor activity, sequence-specific DNA binding | 31 | 4.4E−02 | E2F7, SOX2, TP63, ZIC1, BARX1, HOXC8, FOXD1, PITX1, TRIM29, SIX2, DLX2, FOXE1, TBX18, TCF15 | |
KEGG | Metabolism of xenobiotics by cytochrome P450 | 15 | 2.8E−10 | GSTA1, CYP2S1, ADH7, UGT1A1, ALDH3A1, GSTM3, UGT1A8, UGT1A3, UGT2A1, AKR1C1 | |
KEGG | Neuroactive ligand-receptor interaction | 14 | 5.5E−03 | GABRR1, PTH2R, CHRM3, P2RY1, S1PR5, LPAR3, GPR50, CHRNB2, ADRA2B, HTR2C, GABRQ | |
KEGG | Drug metabolism—cytochrome P450 | 12 | 1.4E−07 | GSTA1, UGT1A7, UGT1A10, GSTM3, UGT1A9, UGT2A1, ADH7, UGT1A1, ALDH3A1 |
Category | Term | Count | p value | Genes |
---|---|---|---|---|
BP | Cell adhesion | 6 | 3.6E−02 | CLCA2, COL7A1, PKP1, ADAM23, DSC3, COL4A6 |
BP | Embryonic limb morphogenesis | 5 | 1.9E−05 | HOXC10, DLX6, DLX5, BMP7, HOXD10 |
BP | Epithelial cell differentiation | 5 | 1.7E−04 | RHCG, DLX6, DLX5, UPK1B, BMP7 |
CC | Extracellular exosome | 20 | 1.5E−02 | COCH, GDA, KRT6B, LGALS7, KRT13, CALB1, A2ML1, LGALS7B, CD19, KRT74, NEB, PKP1, KRT5, RHCG, CALML3, DSG3, UPK1B, MS4A1, SPRR3, SERPINB13 |
CC | Integral component of plasma membrane | 12 | 2.7E−02 | EPHA7, CLCA2, CD19, SLCO1A2, RHCG, ADAM23, PTPRZ1, GABRA3, CDHR1, NTRK2, UPK1B, MS4A1 |
CC | Keratin filament | 4 | 7.8E−03 | KRT74, KRT6B, KRT5, KRT13 |
MF | Calcium ion binding | 8 | 3.1E−02 | CALML3, DSG3, CDHR1, NELL2, DSC3, CALB1, PCDH19, CACNA1B |
MF | Sequence-specific DNA binding | 7 | 2.2E−02 | HOXC10, DLX6, SOX2, FOXE1, DMRT2, HOXD10, HOXD11 |
MF | Structural molecule activity | 6 | 3.8E−03 | KRT74, KRT5, SPRR2A, UPK1B, SPRR3, KRT13 |
KEGG | GABAergic synapse | 3 | 3.8E−02 | GABRA3, HAP1, CACNA1B |