Table 3.
Pathway enrichment using the KEGG, Reactome, and DisGeNET databases. Several pathways significantly enriched with an adjusted p value < 0.2 (FDR < 20%) were identified for the thirty-seven dysregulated bone miRNAs. The top targeted genes most commonly present in the identified pathways are highlighted in bold (16 genes).
| Database | Pathway | Hits | p-Value | FDR |
|---|---|---|---|---|
| KEGG | Focal adhesion | CRK; THBS1; CCND1; CCND2; CRKL; IGF1R; VEGFA; JUN; FLNA; DIAPH1; PAK2; ACTG1 | 6.1 × 10−6 | 1.9 × 10−4 |
| TGF-beta signaling | EP300; THBS1; SMAD3; SP1; SMAD2; BMPR2 | 6.4 × 10−4 | 0.0076 | |
| Neurotrophin signaling | CRK; YWHAG; CRKL; JUN; YWHAQ; IRS4; YWHAB | 8.9 × 10−4 | 0.0076 | |
| Adherens junction | IGF1R; SMAD3; SMAD2; ACTG1 | 0.012 | 0.059 | |
| MAPK signaling | CRK; CRKL; JUN; FLNA; RAPGEF2; ELK4; HSPA1B; PAK2 | 0.019 | 0.080 | |
| Reactome | Cellular Senescence | CDK6; CDKN1B; E2F3; JUN; TNRC6A; SP1; AGO1; TNRC6B; CBX6; MDM2 | 9.6 × 10−6 | 1.1 × 10−4 |
| Signaling by NOTCH | EP300; CCND1; E2F3; TNRC6A; NOTCH2; AGO1; TNRC6B | 8.7 × 10−5 | 6.2 × 10−4 | |
| Signaling by TGF-beta Receptor Complex | CCNT2; SMAD3; SP1; SMAD2; XPO1; PARP1 | 2.5 × 10−4 | 0.0015 | |
| NGF signaling via TRKA | CDKN1B; CRK; CRKL; TNRC6A; AGO1; TNRC6B; MDM2; YWHAB | 0.0023 | 0.0074 | |
| VEGFA-VEGFR2 Pathway | CRK; VEGFA; PAK2; ACTG1; YWHAB | 0.0056 | 0.010 | |
| Signaling by SCF-KIT | CDKN1B; TNRC6A; AGO1; TNRC6B; MDM2; YWHAB | 0.0060 | 0.010 | |
| Signaling by NGF | CDKN1B; CRK; BCL2L11; CRKL; TNRC6A; AGO1; TNRC6B; MDM2; YWHAB | 0.0066 | 0.011 | |
| PI3K/AKT activation | CDKN1B; TNRC6A; AGO1; TNRC6B; MDM2 | 0.0070 | 0.011 | |
| DAP12 signaling | CDKN1B; TNRC6A; AGO1; TNRC6B; MDM2; YWHAB | 0.012 | 0.013 | |
| Signaling by EGFR | CDKN1B; TNRC6A; AGO1; TNRC6B; MDM2; YWHAB | 0.018 | 0.018 | |
| DisGeNET | Acro-Osteolysis | NOTCH2; ATL3 | 0.0029 | 0.010 |
| Pathological fracture | CCND1; NOTCH2 | 0.0066 | 0.010 |