Table 2.
Relevant highest scoring KEGG pathways modulated by miRNAs differentially expressed in trained (TRA) vs sedentary (SED) vastus lateralis (VL).
| KEGG Name | Overlap | p Value | Adjusted p Value | Differentially Expressed miRNA Target Genes | Number of Target Genes Modulated by miRNAs versus Total Differentially Expressed Genes [7] in the Pathway |
|---|---|---|---|---|---|
| Cell cycle | 27/124 | 5.63 × 10−8 | 1.74 × 10−5 | RB1;YWHAE;GSK3B;CDKN1A;CUL1;ORC4;CCNB1;CCND2;CCND1;RAD21;ORC2;E2F1;EP300;E2F3;YWHAH;CREBBP;SMAD4;SMAD3;SMC1A;YWHAZ;STAG2;RBL1;TFDP2;ATM;TP53;MAD1L1;ANAPC1 | 27/54 (50%) |
| AMPK signaling pathway | 21/120 | 4.05 × 10−4 | 4.16 × 10−5 | RAB2A;CPT1A;PRKAA2;STRADB;PPP2R2A;IGF1;PPP2R5C;ADIPOR2;MTOR;CAMKK2;RPTOR;RAB10;CCND1;RPS6KB1;PPP2R5E;SCD;EIF4EBP1;ULK1;PPARG;MAP3K7;PFKP | 21/66 (31%) |
| TGF-beta signaling pathway | 16/90 | 7.74 × 10−6 | 1.59 × 10−4 | CREBBP;SMAD4;SMAD3;CUL1;BMP8B;ACVR1B;SMAD6;RHOA;RGMA;TGFBR2;BMP2;RBL1;RPS6KB1;ID4;EP300;BMPR1A | 16/43 (37%) |
| Thyroid hormone signaling pathway | 19/116 | 3.98 × 10−6 | 1.36 × 10−4 | GSK3B;MAP2K1;CREBBP;THRA;NCOA3;ATP2A2;ATP1B3;SLC16A10;ATP1A2;MTOR;MED12;CCND1;TBC1D4;PLCG2;PLCE1;EP300;RAF1;TP53;PFKP | 19/64 (29%) |
| p53 signaling pathway | 13/72 | 4.58 × 10−5 | 5.23 × 10−4 | CDKN1A;PTEN;IGF1;CCNB1;CCND2;CCND1;SESN3;CCNG1;BCL2;FAS;ATM;MDM4;TP53 | 13/38 (29%) |
| Focal adhesion | 27/199 | 1.91 × 10−6 | 9.79 × 10−5 | GSK3B;FLT1;ROCK2;PTEN;THBS2;ARHGAP35;MYLK3;CRKL;PPP1CB;MAPK8;CCND2;CCND1;FLNA;PAK2;PDGFRA;MAP2K1;PPP1R12A;CAV1;ITGA1;IGF1;RHOA;VEGFA;RAPGEF1;BCL2;GRB2;RAF1;VCL | 27/105 (25%) |
| FoxO signaling pathway | 20/132 | 7.60 × 10−6 | 1.67 × 10−4 | GABARAPL1;MAP2K1;CREBBP;SMAD4;CDKN1A;SMAD3;PRKAA2;PTEN;IGF1;MAPK14;SOD2;TGFBR2;CCNB1;MAPK8;CCND2;CCND1;EP300;GRB2;ATM;RAF1 | 20/63 (31%) |
| Cellular senescence | 23/160 | 4.05 × 10−6 | 1.25 × 10−4 | RB1;MAP2K1;CDKN1A;SMAD3;TRAF3IP2;PTEN;MAPK14;MTOR;TGFBR2;PPP1CB;CCNB1;CCND2;RBL1;CCND1;RBBP4;EIF4EBP1;E2F1;ATM;E2F3;BTRC;RAF1;TP53;PPID | 23/81 (28%) |
| Hippo signaling pathway | 23/160 | 4.05 × 10−6 | 1.14 × 10−4 | YWHAE;GSK3B;TCF7L2;SMAD4;SMAD3;FZD5;FZD9;BMP8B;PPP2R2A;LIMD1;YWHAZ;AMOT;TGFBR2;PPP1CB;BMP2;CCND2;LATS2;CCND1;DVL3;BTRC;TEAD1;BMPR1A;YWHAH | 23/71 (32%) |
| Mitophagy | 12/65 | 7.12 × 10−5 | 7.31 × 10−4 | BECN1;BCL2L13;GABARAPL1;USP15;MAPK8;CSNK2A1;UBB;ATG9A;E2F1;MITF;ULK1;TP53 | 12/33 (36%) |
| mTOR signaling pathway | 22/152 | 5.83 × 10−6 | 1.38 × 10−4 | GSK3B;MAP2K1;PRKAA2;FZD5;STRADB;FZD9;PTEN;IGF1;RHOA;MTOR;RPTOR;FLCN;SLC7A5;CLIP1;RPS6KB1;EIF4EBP1;DVL3;ULK1;GRB2;RICTOR;RAF1;ATP6V1F | 22/72 (30%) |
| Autophagy | 19/128 | 1.72 × 10−5 | 2.79 × 10−4 | BECN1;GABARAPL1;MAP2K1;MTMR3;PRKAA2;ATG9A;PTEN;MTOR;CAMKK2;ERN1;RPTOR;MAPK8;RPS6KB1;LAMP2;ATG2A;BCL2;ULK1;RAF1;MAP3K7 | 19/66 (28%) |
| Adherens junction | 12/72 | 1.98 × 10−4 | 1.56 × 10−3 | TCF7L2;CREBBP;SMAD4;SMAD3;CSNK2A1;EP300;WASL;MAP3K7;PTPRF;RHOA;VCL;TGFBR2 | 12/41 (41%) |
| Longevity regulating pathway | 15/102 | 1.44 × 10−4 | 1.23 × 10−3 | PRKAA2;CLPB;IGF1;SOD2;ADIPOR2;MTOR;CAMKK2;RPTOR;SESN3;RPS6KB1;EIF4EBP1;ULK1;PPARG;TP53;APPL1 | 15/48 (31%) |
| Insulin signaling pathway | 18/137 | 1.44 × 10−4 | 1.20 × 10−3 | GSK3B;PYGB;MAP2K1;PRKAA2;PHKA1;PTPRF;HK2;MTOR;CRKL;PPP1CB;RPTOR;MAPK8;RPS6KB1;PRKAR2A;EIF4EBP1;RAPGEF1;GRB2;RAF1 | 18/80 (22%) |
| Wnt signaling pathway | 20/158 | 1.07 × 10−4 | 1.03 × 10−3 | GSK3B;TCF7L2;CREBBP;SMAD4;SMAD3;CSNK2A1;FZD5;ROCK2;CUL1;FZD9;PRICKLE1;RHOA;MAPK8;CCND2;CCND1;EP300;DVL3;BTRC;MAP3K7;TP53 | 20/73 (27%) |
| MAPK signaling pathway | 32/295 | 2.71 × 10−5 | 3.63 × 10−4 | FLT1;CSF1;MAX;CRKL;ELK4;CACNG6;FGF7;MAPK8;STMN1;FLNA;MAP2K7;PAK2;MAP3K7;MAP4K3;MAP3K2;PDGFRA;MEF2C;MAP2K1;IGF1;IRAK4;MAPK14;VEGFA;TGFBR2;PPM1A;TAOK1;KIT;NF1;FAS;GRB2;RAF1;TP53;MAP3K12 | 32/134 (23%) |
| Neurotrophin signaling pathway | 16/119 | 2.54 × 10−4 | 1.86 × 10−3 | YWHAE;GSK3B;MAP2K1;IRAK4;MAPK14;RHOA;CRKL;MAPK8;PLCG2;BCL2;RAPGEF1;GRB2;RAF1;MAP2K7;TP53;NFKBIB | 16/56 (28%) |
| Sphingolipid signaling pathway | 16/119 | 2.54 × 10−4 | 1.82 × 10−3 | MAP2K1;ABCC1;ROCK2;PTEN;PPP2R2A;PPP2R5C;MAPK14;RHOA;GNA13;MAPK8;SPTLC2;PPP2R5E;BCL2;DEGS1;RAF1;TP53 | 16/61 (26%) |
| HIF-1 signaling pathway | 14/100 | 3.98 × 10−4 | 2.56 × 10−3 | MAP2K1;CREBBP;CDKN1A;FLT1;CUL2;IGF1;HK2;MTOR;VEGFA;RPS6KB1;EIF4EBP1;PLCG2;BCL2;EP300 | 14/54 (26%) |
| mRNA surveillance pathway | 13/91 | 5.21 × 10−4 | 3.15 × 10−3 | HBS1L;SMG1;CPSF7;CPSF2;CSTF2T;PPP2R2A;MSI2;PPP2R5C;MAGOHB;PPP1CB;DDX39B;PPP2R5E;WDR82 | 13/37 (35%) |
| Ferroptosis | 7/40 | 3.15 × 10−3 | 1.62 × 10−2 | PRNP;MAP1LC3B;PCBP1;LPCAT3;SLC11A2;ACSL3;TP53 | 7/25 (28%) |
| Regulation of actin cytoskeleton | 24/214 | 1.59 × 10−4 | 1.29 × 10−3 | NCKAP1;PDGFRA;MAP2K1;PPP1R12A;ROCK2;RDX;ITGA1;LIMK1;WASL;SSH2;RHOA;ARHGAP35;MYLK3;CRKL;PPP1CB;GNA13;FGF7;PIKFYVE;ARPC3;PIP4K2A;RAF1;PAK2;VCL;PFN2 | 24/110 (24%) |
| Ubiquitin mediated proteolysis | 17/137 | 4.33 × 10−4 | 2.72 × 10−3 | UBE2H;FBXW8;CUL5;UBE2B;FBXW7;MGRN1;CUL3;CUL2;CUL1;HUWE1;UBE4B;UBE2S;UBE2Q2;UBE2N;UBA2;BTRC;ANAPC1 | 17/73 (23%) |
KEGG pathways are listed in descending order of the combined score, which is described as c = log(p) * z, where c = the combined score, p = Fisher exact test p-value, and z = z-score for deviation from expected rank [36]. Kyoto Encyclopedia of Genes and Genomes (KEGG, Release 91.0, 1 July 2019) was used. KEGG pathways in bold are also found within the highest scoring ones characterizing the set of differentially expressed mRNAs, KEGG pathways in italic are additional ones characterizing differentially regulated pathways or processes [7]. Overlap: No. of differentially expressed miRNA target genes that overlap total genes of the pathway.