Table 4.
Selected miRNAs in oEVs in Stage 1 and 4 and associated pathways and target genes
| miRNAs | KEGG pathway | p-value | Examples Target Genes (Gene Symbol) |
|---|---|---|---|
| hsa-mir-10b-5p | Pyrimidine metabolism | 0.0214 | NME4,NME2,POLR2D,POLR2A,POLR1B,NME1,CMPK1 |
| hsa-miR-423-3p | Fatty acid biosynthesis | 0.0000 | FASN, ACACA |
| Fatty acid metabolism | 0.0000 | FASN, ACACA, ACOX3, FADS2 | |
| hsa-miR-449a | Carbon metabolism | 0.0286 | TKT,GAPDH,GOT1,H6PD,MDH2,RPIA,ENO1,ALDOA,ADH5 |
| HIF-1 signaling pathway | 0.0390 | NFKB1,GAPDH,LTBR,BCL2,ENO1,LDHA,PIK3CA,SLC2A1,MKNK2,ALDOA,SERPINE1 | |
| hsa-miR-375 | Hippo signaling pathway | 0.0000 | YAP1,YWHAG,CCND2,MOB1B,YWHAB,WWC1,AMOT,FZD8,MPP5,FZD4,DLG4, |
| Amino sugar and nucleotide sugar metabolism | 0.0390 | PGM2,CMAS,UXS1,UGP2,HK2 | |
| hsa-miR-24-3p | Fatty acid biosynthesis | 0.0000 | FASN,MCAT,ACACA |
| Vitamin B6 metabolism | 0.0001 | PDXK,PNPO,PHOSPHO2 | |
| Endocytosis | 0.0005 | RNF41,PSD4,CHMP7,VPS45,SMAD2,CBL,DNM2,FGFR3,VTA1,AGAP3,CAV1,AP2B1,N | |
| Hippo signaling pathway | 0.0014 | ACTB,GSK3B,FZD5,YWHAH,SMAD2,BTRC,APC,NF2,YWHAG,SMAD3,WWTR1,TGFB1, | |
| Bacterial invasion of epithelial cells | 0.0078 | ACTB,ITGB1,CBL,DNM2,PIK3CB,CAV1,PXN,BCAR1,CLTC,CD2AP,CAV2,CTTN,PTK2, | |
| TGF-beta signaling pathway | 0.0228 | SMAD2,ACVR1B,SMAD3,TGFB1,SKP1,MYC,EP300,IFNG,E2F4,CREBBP,TGFBR2,BMP4, | |
| Glycosaminoglycan biosynthesis - heparan sulfate / heparin | 0.0343 | HS6ST2,NDST1,HS6ST1,EXTL3,HS2ST1,HS6ST3 | |
| DNA replication | 0.0343 | CNA,FEN1,MCM4,MCM5,MCM7,RNASEH1,PRIM1,POLA1 | |
| RNA degradation | 0.0423 | PDCP1A,CNOT6,TOB2,CNOT4,DDX6,HSPD1,EXOSC3,EXOSC1,BTG2,DCP2,RQCD1, | |
| hsa-miR-429 | Axon guidance | 0.0009 | PAK2,PPP3R1,RHOA,KRAS,PPP3CA,PTK2,CFL2,RAC1,LIMK1,EFNA1 |
| Fc gamma R-mediated phagocytosis | 0.0350 | CRKL,CRK,WASF3,PLCG1,CFL2,RAC1,LIMK1,ARF6 | |
| Steroid biosynthesis | 0.0000 | SC5D,MSMO1,DHCR24,LSS,FDFT1,LIPA | |
| Antigen processing and presentation | 0.0019 | B2M,IFI30,HSPA4,HSP90AA1,HLA-C,HLA-B,NFYA,PSME2,CANX,PDIA3,HSPA8, | |
| Progesterone-mediated oocyte maturation | 0.0039 | ADCY1,CCNB1,PGR,ADCY7,CCNA2,CDC25B,CPEB4,HSP90AA1,PDE3A,RAF1, | |
| Gap junction | 0.0346 | ADCY1,ADCY7,GNAS,MAP2K5,RAF1,TUBB,TUBB6,CDK1,KRAS,TUBA8,GNA11 | |
| hsa-miR-34b-3p | Glycosaminoglycan degradation | 0.0000 | GNS,IDS,GLB1 |
| hsa-miR-200b-3p | Ras signaling pathway | 0.0043 | KSR1,RASA2,SHC1,PAK2,ETS1,RALBP1,PLD1,RHOA,KRAS,PLCG1,REL,FLT1, |
| Neurotrophin signaling pathway | 0.0273 | CRKL,CRK,SHC1,FRS2,BCL2,RHOA,KRAS,RPS6KA5,PLCG1,JUN,KIDINS220 | |
| hsa-miR-92a-3p | Cell cycle | 0.0000 | GSK3B,PCNA,SMC1A,CCNB1,SMAD2,HDAC1,CCND2,DBF4,SMC3,CDKN1B, |
| Adherens junction | 0.0000 | ACTB,TGFBR1,WASL,SMAD2,IQGAP1,IGF1R,VCL,FYN,MLLT4,NLK,CDH1,S | |
| Thyroid hormone signaling pathway | 0.0011 | ACTB,GSK3B,PRKCA,MED13L,NRAS,RCAN1,PIK3CB,HDAC1,MED13,NOTCH2 | |
| FoxO signaling pathway | 0.0024 | IRS2,BRAF,STAT3,TGFBR1,CCNB1,SMAD2,NRAS,STK4,GABARAPL2,PIK3CB,SETD7 | |
| RNA transport | 0.0025 | SAP18,GEMIN6,NUP153,TGS1,NUP210,XPOT,EIF3B,ELAC2,RPP14,EIF2S3,RNPS1 | |
| p53 signaling pathway | 0.0045 | CCNB1,BID,THBS1,CCND2,CDK1,GADD45A,CDK6,CHEK1,ATM,CCND1,CCNE2,SHISA5 | |
| Signaling pathways regulating pluripotency of stem cells | 0.0178 | PCGF6,JARID2,TCF3,GSK3B,STAT3,KAT6A,SMAD2,NRAS,INHBB,PIK3CB,WNT5A,TBX3 | |
| Protein processing in endoplasmic reticulum | 0.0179 | HSPA1A,EIF2AK1,RAD23B,ERO1L,NPLOC4,SEL1L,UBQLN1,SEC23A,SSR2,P4HB,XBP1 | |
| Notch signaling pathway | 0.0190 | HDAC1,CTBP1,DTX2,NOTCH2,HES1,HDAC2,KAT2A,RBPJ,KAT2B,EP300,CREBBP,MAML1 | |
| Spliceosome | 0.0210 | HSPA1A,LSM7,DDX23,SRSF5,PPIL1,U2SURP,EFTUD2,SF3B1,U2AF2,SNRPE,SF3A3 | |
| MAPK signaling pathway | 0.0210 | BRAF,DUSP4,PRKCA,HSPA1A,TGFBR1,NFKB1,NRAS,CRKL,STK4,ELK4,CRK,DUSP6 | |
| Wnt signaling pathway | 0.0386 | GSK3B,PRKCA,LRP6,TBL1X,BTRC,VANGL1,WNT5A,CTBP1,CCND2,FZD6,AXIN1,SKP1 | |
| Focal adhesion | 0.0393 | BRAF,ACTB,GSK3B,PRKCA,ITGB8,CRKL,CRK,THBS1,ITGA8,PIK3CB,PIP5K1C,PPP1CC | |
| Biosynthesis of amino acids | 0.0473 | TKT,BCAT2,GAPDH,PHGDH,TALDO1,PKM,SHMT2,BCAT1,MTR,ENO1,GOT2,PFKM,ASS1 | |
| hsa-miR-151a-3p | Biosynthesis of unsaturated fatty acids | 0.0000 | PTPLB,ELOVL5,SCD |
| Fatty acid metabolism | 0.0003 | HADH, PTPLB,ACACA,SCD,ELOVL5 | |
| hsa-miR-30d-5p | Mucin type O-Glycan biosynthesis | 0.0000 | GALNT7,B4GALT5,ST3GAL1,GALNT6,GCNT3,GALNT1,GALNT3,GALNT2 |
| Oocyte meiosis | 0.0000 | FBXO5,CAMK2D,PGR,BTRC,CALM1,CPEB4,YWHAG,PPP1CC,PPP3R1 | |
| Ubiquitin mediated proteolysis | 0.0000 | UBE2R2,BTRC,FBXW7,TRIM37,CUL2,NEDD4L,FZR1,PRPF19,MAP3K1 | |
| mRNA surveillance pathway | 0.0317 | MSI2,SAP18,PPP2R3A,EIF4A3,HBS1L,PPP1CC,CPSF2,CPSF6,PAPOLA | |
| hsa-miR-125b-5p | ErbB signaling pathway | 0.0016 | PRKCA,ERBB2,NRAS,CRKL,CRK,PAK2,RAF1,CDKN1B,EIF4EBP1,ERBB3 |
| Regulation of actin cytoskeleton | 0.0135 | SSH2,EZR,NRAS,CRKL,CRK,PIP5K1C,PAK2,ARHGEF12,PPP1CC,ACTG1 |
Table shows selected miRNAs based on differential expression and high abundance in EVs in Stage 1 and Stage 4 and associated representative pathways and target genes