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Table 3 Gene sets with strongest overlaps with observed differentially expressed genes.*

From: Tungsten carbide cobalt nanoparticles exert hypoxia-like effects on the gene expression level in human keratinocytes

up-regulated gene sets

description

WC 3 h

WCCo 3 h

CoCl2 3 h

WC 3 d

WCCo 3 d

CoCl2 3 d

hypoxia related gene sets

       

HIF1_TARGETS

Hif-1 (hypoxia-inducible factor 1) transcriptional targets

 

0.17

  

0.01

 

HIFPATHWAY

BIOCARTA: Under normal conditions, HIF-1 is degraded; under hypoxic conditions, it activates transcription of genes controlled by hypoxic response elements (HREs)

    

0.02

0.20

HYPOXIA_FIBRO_UP

Up-regulated by hypoxia in normal fibroblasts from both young and old donors

 

0.20

 

0.65

0.05

 

HYPOXIA_NORMAL_UP

Up-regulated by hypoxia in normal, RPTEC renal cells

 

0.50

  

0.02

 

HYPOXIA_REG_UP

Up-regulated by hypoxia in renal cells, and down-regulated with reoxygenation

 

0.05

  

0.01

0.03

HYPOXIA_REVIEW

Genes known to be induced by hypoxia

 

0.22

 

0.75

0.00

 

MANALO_HYPOXIA_UP

Genes up-regulated in human pulmonary endothelial cells under hypoxic conditions or after exposure to AdCA5, an adenovirus carrying constitutively active hypoxia-inducible factor 1 (HIF-1alpha)

 

0.24

  

0.01

0.21

MENSE_HYPOXIA_UP

List of Hypoxia-induced genes found in both Astrocytes and HeLa Cell

 

0.00

  

0.02

0.13

RESPONSE_TO_HYPOXIA

GO:0001666. Change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating lowered oxygen tension

    

0.12

0.08

carbohydrate metabolism

       

POLYSACCHARIDE_METABOLIC_PROCESS

GO:0005976. Chemical reactions and pathways involving polysaccharides, a polymer of more than 10 monosaccharide residues joined by glycosidic linkages

    

0.06

 

FRUCTOSE_AND_MANNOSE_METABOLISM

Genes involved in fructose and mannose metabolism

 

0.21

  

0.02

 

HSA00010_GLYCOLYSIS_AND_ GLUCONEOGENESIS

KEGG: Genes involved in glycolysis and gluconeogenesis

    

0.00

0.14

GLYCOGEN_METABOLISM

Genes involved in glycogen metabolism

    

0.04

 

GALACTOSE_METABOLISM

Genes involved in galactose metabolism

    

0.04

 

PENTOSE_PHOSPHATE_PATHWAY

Genes involved in pentose phosphate pathway

   

0.61

0.14

 

STARCH_AND_SUCROSE_ METABOLISM

Genes involved in starch and sucrose metabolism

    

0.01

0.50

endocrine metabolism

       

GN_CAMP_GRANULOSA_UP

Up-regulated in human granulosa cells by the gonadotropins LH and FSH, as well as by cAMP- stimulator forskolin

    

0.01

0.17

LH_GRANULOSA_UP

Up-regulated in human granulosa cells stimulated with luteinizing hormone (LH)

    

0.01

 

FSH_GRANULOSA_UP

Up-regulated in human granulosa cells stimulated with follicle stimulation hormone (FSH)

    

0.01

 

BREAST_CANCER_ESTROGEN_SIGNALING

Genes preferentially expressed in breast cancers, especially those involved in estrogen-receptor- dependent signal transduction

    

0.05

 

PROSTAGLANDIN_SYNTHESIS_ REGULATION

WIKIPATHWAYS: Prostaglandin Synthesis and Regulation

 

0.09

    

HSA04150_MTOR_SIGNALING_ PATHWAY

KEGG: Genes involved in mTOR signalling pathway

 

0.19

    

cell adhesion, structure, cytoskeleton

       

HSA04510_FOCAL_ADHESION

KEGG: Genes involved in focal adhesion

    

0.07

0.46

ACTIN_CYTOSKELETON

GO:0015629. Part of the cytoskeleton (the internal framework of a cell) composed of actin and associated proteins

    

0.04

 

ACTIN_BINDING

GO:0003779. Interacting selectively with monomeric or multimeric forms of actin, including actin Filaments

    

0.06

 

CYTOSKELETON_DEPENDENT_ INTRACELLULAR_TRANSPORT

GO:0030705. The directed movement of substances along cytoskeletal elements such as microfilaments or microtubules within a cell

    

0.07

 

ANATOMICAL_STRUCTURE_FORMATION

GO:0048646. Process pertaining to the initial formation of an anatomical structure from unspecified parts

    

0.04

 

VASCULATURE_DEVELOPMENT

GO:0001944. Process whose specific outcome is the progression of the vasculature over time, from its formation to the mature structure

    

0.04

 

ANGIOGENESIS

GO:0001525. Blood vessel formation when new vessels emerge from the proliferation of pre-existing blood vessels

    

0.05

 

HSA04512_ECM_ RECEPTOR_INTERACTION

KEGG: Genes involved in ECM-receptor interaction

    

0.06

0.29

miscellaneous

       

G13_SIGNALING_PATHWAY

G13 signaling pathway

    

0.10

0.51

NUCLEOTIDE_BIOSYNTHETIC_PROCESS

GO:0009165. Chemical reactions and pathways resulting in the formation of nucleotides

    

0.09

 

CARBON_CARBON_LYASE_ACTIVITY

GO:0016830. Catalysis of the cleavage of C-C bonds by other means than by hydrolysis or oxidation, or conversely adding a group to a double bond

    

0.10

 

ALKPATHWAY

Activin receptor-like kinase 3 (ALK3) is required during gestation for cardiac muscle development

     

0.29

CARDIACEGFPATHWAY

BIOCARTA: Cardiac hypertrophy, a response to high blood pressure, is stimulated by GPCR ligands such as angiotensin II that activate the EGF pathway

 

0.21

  

0.01

 

WNT_SIGNALING

Wnt signaling genes

    

0.01

 

HSA05211_RENAL_CELL_CARCINOMA

Genes involved in renal cell carcinoma

    

0.07

 

NKTPATHWAY

BIOCARTA: T cell differentiation into Th1 and Th2 cells occurs by differential chemokine receptor expression, which mediates tissue localization and immune response

     

0.29

BIOGENIC_AMINE_SYNTHESIS

WIKIPATHWAYS: Genes involved in synthesis of biogenic amines

 

0.23

    

HSA00591_LINOLEIC_ACID_METABOLISM

Genes involved in linoleic acid metabolism

 

0.22

    

HSA00361_GAMMA_HEXACHLOROCYCLOHEXANE_DEGRADATION

KEGG: Genes involved in gamma-hexachlorocyclohexane degradation

 

0.17

    

down-regulated gene sets

description

WC 3 h

WCCo 3 h

CoCl2 3 h

WC 3 d

WCCo 3 d

CoCl2 3 d

RNA metabolism and processing

       

MRNA_METABOLIC_PROCESS

GO:0016071. Chemical reactions and pathways involving mRNA

 

0.23

    

RIBONUCLEOPROTEIN_COMPLEX_

GO:0022613. The cellular process by which a complex containing RNA and proteins, is synthesized,

 

0.25

    

BIOGENESIS_AND_ASSEMBLY

aggregates, and bonds together

      

RNA_PROCESSING

GO:0006396. Any process involved in the conversion of one or more primary RNA transcripts into one or more mature RNA molecules

 

0.20

    

RNA_SPLICING__VIA_TRANSESTERIFICATION_ REACTIONS

GO:0000375. Splicing of RNA via a series of two transesterification reactions

 

0.20

    

SEQUENCE_SPECIFIC_ DNA_BINDING

GO:0043565. Interacting selectively with DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA e.g. promotor binding or rDNA binding

 

0.33

    

TRNA_METABOLIC_PROCESS

GO:0006399. Chemical reactions and pathways involving tRNA

 

0.27

    

nucleus and the nuclear membrane related gene sets

       

PORE_COMPLEX

GO:0046930. Any small opening in a membrane that allows the passage of gases and/or liquids.

 

0.28

    

NUCLEAR_PORE

GO:0005643. Any of the numerous similar discrete openings in the nuclear envelope of a eukaryotic cell, where the inner and outer nuclear membranes are joined

 

0.19

    

NUCLEAR_LUMEN

GO:0031981. The volume enclosed by the nuclear inner membrane

 

0.31

    

NUCLEAR_MEMBRANE

GO:0031965. Either of the lipid bilayers that surround the nucleus and form the nuclear envelope; excludes the intermembrane space

 

0.31

    

enzyme and receptor activity

       

UBIQUITIN_PROTEIN_ LIGASE_ACTIVITY

GO:0004842. Catalysis of the reaction: ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine

 

0.32

    

SMALL_PROTEIN_CONJUGATING_ ENZYME_ACTIVITY

GO:0008639. Catalysis of the covalent attachment of small proteins, such as ubiquitin or ubiquitin-like proteins, to lysine residues on a target protein. This function may be performed alone or in conjunction with an E3, ubiquitin-like protein ligase

 

0.21

    

CASPASEPATHWAY

BIOCARTA: Caspases are cysteine proteases active in apoptosis

   

0.30

  
  1. * identified by GSEA (gene set enrichment analysis), using the databases MSigDB C2 and C5; number of entries is limited to gene sets with a false discovery rate (FDR) < 0.35 in at least one of the treatments and FDR < 0.1 for the WC-Co 3 d treatment; only gene sets obviously related to biochemical pathways or cellular organelles were selected; full table provided as Additional File 3