Table 3.
Potential effects of the microRNAs comprised in the OT-CR differential profile on the different targets of the death receptor pathway.
| microRNA | Level of microRNA in OT vs. CR | Targets | Potential effects of the microRNA on targets OT x CR | Function of target molecules | Potential differential microRNA effects in OT vs. CR |
|---|---|---|---|---|---|
| miR-27a-5p | OT > CR | RIPK1 (Receptor interacting serine/threonine kinase 1) | <RPK1 (OT) >RPK1 (CR) | Kinase involved in the transduction of necroptosis signals (25) | Decreased death stimulus in OT than in CR |
| BCL2* | <BCL2 (OT) >BCL2 (CR) | Positive cell survival regulator (26) | Increased cell survival in CR | ||
| TL1 (TNFSF15) TNF superfamily member 15 | <TNFS15(OT) >TNFS15(CR) | Can activate NF-kB (27) | Lower expression of pro-inflammatory and cell survival genes in OT | ||
| miR-331-3p | OT > CR | TL1 (TNFSF15) (TNF superfamily member 15) | <TNFS15(OT) >TNFS15(CR) | Can activate NF-kB (27) | Lower expression of pro-inflammatory and cell survival genes in OT |
| TNF (tumor necrosis factor) | <TNF (OT) >TNF (RC) | Involved in several proinflammatory responses (27) | Decreased proinflammatory responses in OT | ||
| CASP9 (Caspase 9) | <CASP9(OT) >CASP9(CR) | Activates CASP3 (28) | Decreased cell death in OT than in CR | ||
| miR-885-5p | OT > CR | CRADD/RAIDD (CASP2 and RIPK1 domain containing adaptor with death domain) | <CRADD(TO) >CRADD(CR) | Induces DNA fragmentation (29) | Decreased cell death in OT than in CR |
| CASP3* (Caspase 3) | <CASP3 (OT) >CASP3(CR) | Induces DNA fragmentation and condensation (30) | Decreased cell death in OT than in CR | ||
| miR-1260a | OT < CR | TL1 (TNFSF15) TNF superfamily member 15 | >TNFS15 (OT) < TNFS15(CR) | Can activate NF-kB (27) | Higher expression of pro-inflammatory and cell survival genes in OT |
| DAXX (Death domain associated protein) | >DAXX (OT) < DAXX (CR) | Interacts with FAS that is involved in promoting apoptosis (31) | Induction of apoptosis in OT | ||
| MAP3K5 (ASK1) Mitogen-activated protein kinase kinase kinase 5 | >MAP3K5(OT) < MAP3K5(CR) | Activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (32) | Increased propagation of the signals of the MAP3K5 pathway in OT | ||
| BCL2 | >BCL2 (OT) < BCL2 (CR) | Positive cell survival regulator (26) | Increased cell survival in OT | ||
| miR-638 | OT < CR | TNF (tumor necrosis factor) | >TNF (OT) < TNF (CR) | Involved in several proinflammatory responses (27) | Increased proinflammatory responses in OT |
| TBK1 (TANK-binding kinase 1) | >TBK1 (OT) < TBK1 (RC) | Can activate NF-kB (33) | Higher expression of pro-inflammatory and cell survival genes in OT | ||
| miR-1233-3p | OT < CR | TL1 (TNFSF15) TNF superfamily member 15 | >TNFS15(OT) < TNFS15(RC) | Can activate NF-kB (27) | Higher expression of pro-inflammatory and cell survival genes in OT |
| DFFB (DNA fragmentation factor subunit beta) | >DFFB (OT) < DFFB (RC) | Involved in promoting cell death (34) | Increased cell death in OT than in CR |
(>) higher; (< ) lower, comparing OT vs. CR. OT, Operational Tolerance; CR, Chronic rejection.
*
Targets experimentally observed in cell death pathways.