Table III.
GO enrichment analysis for target genes of DE-miRNAs in exosomes of serum from healthy children, patients with KD and patients with KD patients following IVIG therapy.
| A, Target genes of DE-miRNAs | ||
|---|---|---|
| Term | P-value | Genes |
| GO:0045893, positive regulation of transcription, DNA-templated | 1.39×10−5 | PPARD, GDF2, MITF, ZXDC, TGFB3, NFKB1, CTCF, GLI3, LGR4, ZIC3, WNT4, RRN3, ZNF281, TBL1XR1, EGR2, FOXJ2, SOX11, MED14, RB1, ESR2, MED13, SIX4, HIPK2, MAPK3, ZNF711, TFAP2B, ERBB4, HOXA11, SOX2, EHF, CDH1, NFYA, TFAM, NR1D2, NPAT, CREBL2, KLF6, IL5, TRIP4, TBX3, SMAD4, IGF1, MSTN, CREB5, ATMIN, FZD4, RLF, YWHAH, SFRP1, SP1, SETD7, NEUROD1, TP53INP2, F2R |
| GO:0045944, positive regulation of transcription from RNA polymerase II promoter | 1.05×10−3 | CCNT2, HLF, GDF2, RNASEL, E2F8, STAT5B, MITF, EDN1, ARID4B,TGFB3, CTCF, NFKB1, GLI3, ZIC3, ZBTB38, CRX, PGR, PCGF5, ZNF304, SERPINE1, OGT, FGF1, TBL1XR1, SATB2, EXOSC9, EGR2, FOXJ2, SOX11, MTA2, RXRA, MED14, RB1, SIX4, MED13, CD40, GRHL2, GTF2H1, ACVR2A, VEGFA, MAPK3, HIPK2, TFAP2B, TFAP2C, CRTC3, FGFR2, SOX2, ONECUT2, TAF9B, EHF, EGLN1, CDC73, NR2C2, ATF1, TFAM, CHD7, NIPBL, DDX3X, PKD2, MYF6, IKZF4, IKZF1, CEBPD, SMAD4, IGF1, EN2, CSRP3, TET1, PARK7, DDX58, RLF, ATRX, SP1, TRPS1, NEUROD1, IRF2, NHLH2, PBX3, PBX2, FOXI1 |
| GO:0043200, response to amino acid | 1.36×10−3 | ICAM1, SLC1A2, GLRB, MTHFR, CDKN1B, GLRA3, EDN1, CDO1 |
| GO:0043406, positive regulation of MAP kinase activity | 1.49×10−3 | RASGRP1, EDN1, VEGFA, PDE5A, ADRA2A, KITLG, PDGFC, KIT, CD40, FGF1, LRRK2 |
| GO:0043268, positive regulation of potassium ion transport | 1.57×10−3 | DRD1, KIF5B, ADRA2A, STK39, DLG1 |
| GO:0051091, positive regulation of sequence-specific DNA binding transcription factor activity | 2.15×10−3 | IL5, EDN1, TRIM27, TRIM14, TRIM25, ESR2, KIT, FZD4, TRIM21, PARK7, DDX58, TRIM32, HIPK2, NEUROD1, NHLH2 |
| GO:0019228, neuronal action potential | 3.97×10−3 | DRD1, SCN1A, SCN3A, GRIK2, ANK3, KCNA1, SCN9A |
| GO:0014066, regulation of phosphatidylinositol 3-kinase signaling | 4.01×10−3 | FGFR2, C3ORF58, EREG, ERBB4, ERBB3, RASGRP1, MAPK3, KITLG, KIT, FGF1, PIP4K2A, PIP4K2C |
| GO:0050890, cognition | 5.41×10−3 | MAGT1, CHD7, NIPBL, PTCHD1, NF1, CHRNA4, CHRNB2, CHMP2B |
| GO:0007265, Ras protein signal transduction | 5.42×10−3 | ZNF304, PLD1, PLCE1, RASGRP1, NF1, ADRA2A, IGF1, RB1, SHC3, KSR1, PARK7 |
| GO:0014070, response to organic cyclic compound | 5.50×10−3 | ICAM1, CD83, ACSL1, SFRP1, TRPA1, ABCC4, ABCD3, COMT, ATF1 |
| GO:0047496, vesicle transport along microtubule | 6.24×10−3 | DYNC1I1, NDEL1, KIF5B, HTT, RASGRP1 |
| GO:0010842, retina layer formation | 6.48×10−3 | PROM1, HIPK2, FJX1, TFAP2B, CALB1, DSCAM |
| GO:0061024, membrane organization | 7.89×10−3 | YWHAH, RAB14, YWHAB, TBC1D4, PMP2, RAB10, YWHAE |
| GO:0008585, female gonad development | 8.14×10−3 | WNT4, COL9A3, SFRP1, ZFP42, TIPARP |
| GO:0060021, palate development | 9.66×10−3 | WFIKKN2, ACVR2B, SATB2, CHD7, TBX3, TIPARP, TGFB3, SMAD4, COL2A1, C5ORF42, GLI3 |
| GO:0090073, positive regulation of protein homodimerization activity | 1.14×10−2 | CRBN, TIRAP, PARK7, TRAF4 |
| GO:0048565, digestive tract development | 1.22×10−2 | FGFR2, TRPS1, TGFB3, PDGFC, RB1, KIT, LGR4 |
| GO:0007059, chromosome segregation | 1.32×10−2 | CIAO1, NDEL1, DDX3X, PPP1R7, SLC25A5, USP9X, NEK9, CTCF, SRPK1, MIS12 |
| GO:0042552, myelination | 1.34×10−2 | EGR2, TSPAN2, MAL2, ATRN, CMTM8, XK, QKI, ACSBG1 |
| GO:0001764, neuron migration | 1.44×10−2 | SATB2, TUBB2B, USP9X, CELSR1, PCM1, YWHAE, SEMA6A, NDEL1, NAV1, CCR4, NEUROD4, DCX, MYH10 |
| GO:0043154, negative regulation of cysteine-type endopeptidase activity involved in apoptotic process | 1.45×10−2 | ARL6IP1, LAMP3, DDX3X, TNFAIP8, VEGFA, TFAP2B, USP47, RAG1, BIRC5, YWHAE |
| GO:0035136, forelimb morphogenesis | 1.56×10−2 | NIPBL, TBX3, RNF165, TFAP2B |
| GO:0007156, homophilic cell adhesion via plasma membrane adhesion molecules | 1.59×10−2 | PCDHA6, ME2, PCDHA2, CLSTN2, CADM2, PCDH9, CDH1, PTPRT, CELSR1, CDH2, IGSF9B, PCDHAC2, PCDHAC1, CDH9, PCDHA10, ROBO2, DSCAM |
| GO:0043372, positive regulation of CD4-positive, alpha-beta T cell differentiation | 1.74×10−2 | CD83, TNFSF4, SASH3 |
| GO:0010951, negative regulation of endopeptidase activity | 1.80×10−2 | WFIKKN2, C5, CD109, PAPLN, FURIN, A2ML1, WFDC8, SERPINE2, SERPINE1, TFPI, PEBP1, ITIH5, CSTA, CRIM1 |
| GO:0005975, carbohydrate metabolic process | 1.83×10−2 | GALNT3, GANAB, FUT9, GNPDA2, ST8SIA1, GPD1L, MAN2A2, PGM2, PGM3, GANC, ALDH1B1, SLC2A2, AKR1B1, ST8SIA5, FUT4, SPAM1, B4GALT5, PYGB |
| GO:0040007, growth | 1.83×10−2 | OPA3, BMP3, GDF2, VEGFA, BMP8B, FOXP2 |
| GO:0006513, protein monoubiquitination | 1.83×10−2 | TSG101, DTL, KLHL12, RAD18, TRIM25, TRIM21 |
| GO:0001894, tissue homeostasis | 1.93×10−2 | AKR1B1, TRIM32, COL2A1, RB1, TP53INP2 |
| GO:0048745, smooth muscle tissue development | 2.06×10−2 | NF1, TIPARP, DLG1, FOXP2 |
| GO:0046622, positive regulation of organ growth | 2.06×10−2 | ARX, IL7, RAG2, SASH3 |
| GO:0061045, negative regulation of wound healing | 2.06×10−2 | WNT4, HMGCR, SERPINE1, CD109 |
| GO:0007519, skeletal muscle tissue development | 2.28×10−2 | MYF6, CCNT2, CFL2, NF1, SIX4, FLNB, CSRP3, FOXP2 |
| GO:0048839, inner ear development | 2.56×10−2 | CDKN1B, CXCL14, CEBPD, DUOX2, SOX2, TGFB3, NEUROD1 |
| GO:0031954, positive regulation of protein autophosphorylation | 2.73×10−2 | RAP2B, VEGFA, PDGFC, RAD50, CALM2 |
| GO:0097150, neuronal stem cell population maintenance | 2.73×10−2 | SOX2, CDH2, PCM1, HOOK3, MMP24 |
| GO:0033157, regulation of intracellular protein transport | 2.80×10−2 | NDEL1, SH3TC2, LCP1 |
| GO:0021631, optic nerve morphogenesis | 2.80×10−2 | CHRNB2, GLI3, EPHB1 |
| GO:0048511, rhythmic process | 3.03×10−2 | HLF, SP1, NR1D2, SFPQ, PASD1, PRKAA2, NFYA, FBXL3 |
| GO:0070911, global genome nucleotide-excision repair | 3.13×10−2 | SUMO3, UBE2N, DDB2, ERCC4, USP45, GTF2H1 |
| GO:0098609, cell-cell adhesion | 3.13×10−2 | ZC3HAV1, KIF5B, CKAP5, RPL15, YWHAB, TRIM25, ARFIP1, FLNB, YWHAE, PARK7, MMP24, CHMP2B, EIF4G2, GAPVD1, DDX3X, FNBP1L, SERBP1, TMOD3, PCMT1, DNAJB1, MAPRE1, RAB10, UBAP2, AHNAK |
| GO:0039702, viral budding via host ESCRT complex | 3.20×10−2 | CHMP1A, TSG101, CHMP6, VPS37C, CHMP2B |
| GO:0060078, regulation of postsynaptic membrane potential | 3.20×10−2 | SCN1A, SCN3A, PKD2, SCN9A, SCN4B |
| GO:0006366, transcription from RNA polymerase II promoter | 3.28×10−2 | CCNT2, NCBP2, HLF, POLR2E, STAT5B, TAF9B, MITF, SOX2, ONECUT2, NFKB1, EHF, CTCF, NFYA, GLI3, ATF1, ZIC3, CRX, TFAM, MAX, DDX21, VEZF1, MYF6, ZNF831, EGR2, FOXJ2, CEBPD, SOX11, SNAPC3, SMAD4, CREB5, SIX4, GRHL2, GTF2H1, TRPS1, TFAP2B, IRF2, NEUROD1, TFAP2C, PBX3, FOXI1 |
| GO:0006044, N-acetylglucosamine metabolic process | 3.29×10−2 | CHST7, GNPDA2, GNPNAT1, MGEA5 |
| GO:0060134, prepulse inhibition | 3.29×10−2 | DRD1, SLC6A3, NRXN1, CTNNA2 |
| GO:0032897, negative regulation of viral transcription | 3.29×10−2 | TRIM32, TRIM14, TRIM27, TRIM21 |
| GO:0007399, nervous system development | 3.30×10−2 | PCDHA6, GLRB, FUT9, MOBP, PCDHA2, ERBB4, CAMK2G, ARID1B, IGSF9B, GAS7, NR2C2, PCDHAC2, PCDHAC1, SEMA6A, ATXN3, NDEL1, TPP1, VEGFA, MSI1, PCDHA10, DCX, CRIM1, DLG1, WNT8B, DSCAM |
| GO:0045892, negative regulation of transcription, DNA-templated | 3.46×10−2 | PPARD, GCLC, TSG101, CTCF, GLI3, LGR4, ZBTB38, WNT4, ZNF227, NIPBL, NR1D2, GATAD2A, ZNF425, PASD1, CRY1, BAHD1, MYF6, ZNF281, IKZF4, TNFSF4, TBX3, IKZF1, CEBPD, YWHAB, SMAD4, BIRC5, RB1, SIX4, FOXP2, CHMP1A, CDKN1B, SFRP1, TRIM33, EREG, SFPQ, RBAK, USP47, TFAP2B, XCL1 |
| GO:0015758, glucose transport | 3.52×10−2 | PPARD, SLC2A10, SLC2A2, EDN1, SLC2A1, HK2 |
| GO:0051402, neuron apoptotic process | 3.52×10−2 | MAX, USP53, GRIK2, ERBB3, RB1, NLRP1 |
| GO:0006914, autophagy | 3.58×10−2 | TSG101, CHMP6, VPS41, VPS37C, PARK7, VTI1A, CHMP2B, TBC1D25, ATG5, FNBP1L, RB1CC1, ATG4A, LRRK2, VPS39 |
| GO:0050680, negative regulation of epithelial cell proliferation | 3.60×10−2 | FGFR2, PPARD, EREG, SFRP1, SOX2, CDC73, RB1, DLG1 |
| GO:0006479, protein methylation | 3.70×10−2 | PCMTD2, BHMT, PCMT1, ETF1, N6AMT1 |
| GO:0045662, negative regulation of myoblast differentiation | 3.70×10−2 | PPARD, TBX3, CXCL14, MSTN, CSRP3 |
| GO:0046854, phosphatidylinositol phosphorylation | 3.75×10−2 | FGFR2, EREG, ERBB4, ERBB3, PI4K2A, KITLG, PI4K2B, KIT, FGF1, PIP4K2A, PIP4K2C |
| GO:0045787, positive regulation of cell cycle | 3.94×10−2 | FGFR2, ANKRD17, CDKN1B, TBX3, TRIM32, TRIM21 |
| GO:0007585, respiratory gaseous exchange | 3.94×10−2 | HNMT, TMPRSS11D, EDN1, CHRNA4, PBX3, TRAF4 |
| GO:0006813, potassium ion transport | 3.96×10−2 | KCNS3, KCNMA1, KCNS1, CDKN1B, SLC12A2, ATP4B, SLC24A3, KCNA1, KCNA6, KCNJ12 |
| GO:0051260, protein homooligomerization | 4.03×10−2 | CCDC88C, GLRA3, KCNA1, PRND, KCNA6, KCNA7, KCNS3, ANXA6, STOM, KCNS1, CLDN1, KCTD16, ZBTB1, SLC1A1, EHD3, SPAST, KCTD12 |
| GO:0034454, microtubule anchoring at centrosome | 4.05×10−2 | KIF3A, PCM1, HOOK3 |
| GO:0035020, regulation of Rac protein signal transduction | 4.05×10−2 | SSX2IP, OGT, CRK |
| GO:0010606, positive regulation of cytoplasmic mRNA processing body assembly | 4.05×10−2 | CNOT6L, CNOT2, CNOT6 |
| GO:0010960, magnesium ion homeostasis | 4.05×10−2 | ANK3, KCNA1, TFAP2B |
| GO:0071910, determination of liver left/right asymmetry | 4.05×10−2 | PKD2, CCDC39, ZIC3 |
| GO:0045165, cell fate commitment | 4.22×10−2 | FGFR2, WNT4, ERBB4, TRPS1, ONECUT2, NEUROD4, WNT8B |
| GO:0071456, cellular response to hypoxia | 4.24 ×10−2 | ICAM1, PPARD, PTGIS, TBL2, STC2, CPEB2, SFRP1, EDN1, VEGFA, BNIP3L, HIPK2 |
| GO:0032456, endocytic recycling | 4.25×10−2 | STX6, VPS52, RAB14, ARL4C, EHD3 |
| GO:0030307, positive regulation of cell growth | 4.52×10−2 | EIF4G2, EXTL3, EXOSC9, DDX3X, SFRP1, TRIM32, TAF9B, USP47, H3F3B, N6AMT1 |
| GO:0042384, cilium assembly | 4.54×10−2 | KIF3A, DZIP1, ONECUT2, PCM1, C5ORF42, ACTR2, TTC30A, FNBP1L, C10ORF90, ABCC4, SSX2IP, EXOC5, EHD3 |
| GO:0009636, response to toxic substance | 4.81×10−2 | GLYAT, MAPK3, SLC30A4, SLC6A14, SCN9A, CDH1, GUCY2C, HTR1D, NQO1, PON3 |
| GO:2000679, positive regulation of transcription regulatory region DNA binding | 4.82×10−2 | NEUROD1, IGF1, RB1, PARK7 |
| GO:0022408, negative regulation of cell-cell adhesion | 4.82×10−2 | NF2, TNR, EPB41L5, CDH1 |
| GO:0007076, mitotic chromosome condensation | 4.82×10−2 | CHMP1A, NCAPH, NCAPG, CDCA5 |
| GO:0006351, transcription, DNA-templated | 4.96×10−2 | IL16, ZNF451, ZXDC, CNOT2, ZNF250, MED22, CNOT6, ZNF254, PGR, ZNF304, EPC2, MIER3, ZNF445, CRY1, SAMD4B, ZNF449, IKBKAP, SATB2, RXRA, ARID1B, TRIM33, MAPK3, TGIF2, VGLL3, CRTC3, ERBB4, HOXA11, NR2C2, ARX, ZNF227, DDX3X, CNOT6L, ZNF697, ZNF425, ZNF124, CREBL2, IKZF4, KLF6, TRIP4, IKZF1, RFX5, SMAD4, ZNF521, ZNF320, ZNF585A, ZNF627, CSRP3, TET1, FOXP2, ZNF419, ZNF417, PNRC1, JAZF1, ZNF318, PHF6, CCNT2, PPARD, ZNF518B, ZNF81, ARID4B, ZFP42, E2F8, ZNF10, ZBTB38, PCGF5, HIF1AN, BRD9, ZNF281, NFKBIZ, TBL1XR1, ZNF33A, EGR2, ZNF354A, ZNF354C, ZFY, ZFX, SF1, RB1, ESR2, ZBTB26, PURB, GTF2H1, CHMP1A, BRWD1, HIPK2, ZNF711, ZNF480, LIN54, ZNF740, POLR2E, LIN9, SCML2, ZNF660, CHD7, ZSCAN22, NR1D2, RB1CC1, NPAT, GATAD2A, PRKAA2, ZNF470, BAHD1, ZNF267, TBX3, PPHLN1, CEBPD, NLK, ZNF770, ZFP1, ZNF667, TRIM27, BIRC5, ATMIN, ZNF665, RLF, ATRX, ATXN3, SFPQ, RBAK, ZBTB5, NHLH2, ZNF461, SETD7, NEUROD4, PBX2, ZNF766, TP53INP2 |
| GO:0048661, positive regulation of smooth muscle cell proliferation | 4.96×10−2 | FGFR2, EREG, HMGCR, EDN1, AKR1B1, IGF1, ABCC4, CALCRL |
| GO:0045669, positive regulation of osteoblast differentiation | 4.96×10−2 | ACVR2A, WNT4, ACVR2B, GDF2, CEBPD, SOX11, IGF1, GLI3 |
| GO:0000122, negative regulation of transcription from RNA polymerase II promoter | 4.99×10−2 | PPARD, IMPACT, E2F8, EDN1, MITF, CNOT2, NFKB1, CTCF, HSBP1, ZNF254, GLI3, CRY1, DLG1, ZNF281, TBL1XR1, SATB2, SOX11, MTA2, RXRA, HNRNPA2B1, RB1, ESR2, PURB, ACVR2B, TRIM33, VEGFA, HIPK2, TFAP2B, TGIF2, TFAP2C, FGFR2, USP9X, TAF9B, SOX2, CDC73, ARX, NIPBL, GATAD2A, IKZF1, TBX3, RFX5, PTPN2, SMAD4, TRIM27, FOXP2, DLX1, DKK1, SFPQ, TRPS1, JAZF1, IRF2, ZBTB1 |
| B, DEGs regulated by DE-miRNAs | ||
| Term | P-value | Genes |
| GO:0060828, regulation of canonical Wnt signaling pathway | 2.82×10−2 | KREMEN1, LRRK2 |
DE-miRNAs, differentially expressed miRNAs; miRNA, microRNA; GO, Gene Ontology; KD, Kawasaki disease; IVIG, intravenous immunoglobulin; DEGs, differentially expressed genes.