Table 2.
The epigenetic regulation in the development and function of MDSCs.
| Epigenetic modulation | Target gene/pathway | Effect on MDSCs | References |
|---|---|---|---|
| DNA modifications | |||
| THC | STAT3/S100A8 | Promote differentiation and immunosuppressive activity | (53) |
| DAC | IRF8/TNFα | Sustain survival and accumulation | (48) |
| Histone acetylation | |||
| TSA | NOS−/HO- | Promote differentiation/expansion | (49) |
| HDAC2 | Retinoblastoma | Promoted the phenotype conversion | (50) |
| HDAC11 | C/EBPβ | Prevented MDSCs differentiation and function | (51, 52) |
| miRNAs regulation | |||
| miR-9 | Runx1/SOCS3 | Promote differentiation and immunosuppressive activity | (53) (54) |
| miR-10a | AMPK | Promote expansion and activation | (55) |
| miR-21/miR-181 | STAT3, C/EBP, MLL1 | Promote differentiation and immunosuppressive activity | (56, 57) |
| miR-34a | N-myc | Inhibit apoptosis | (58, 59) |
| miRNA-30a | SOCS3 | Increases differentiation and immunosuppressive activity |
(60, 61) |
| miR-125 | JAK/STAT3 | Promote accumulation and immunosuppressive activity | (62) |
| miR-494 | PTEN//PI3K/Akt | Promote accumulation and immunosuppressive activity | (63) |
| miR-210 | Arginase/NO | Enhance immunosuppressive activity | (64) |
| miR-155 | SHIP-1/HIF-1α | Promote expansion and immunosuppressive activity | (65–67) |
| miR-200C | PTEN/FOG2 | Increase immunosuppressive activity | (68) |
| miR-17 family | AML1 | Prevente differentiation and immunosuppressive activity | (69) |
| miR-146a | IRAK1/TRAF6/NF-kB | Inhibit expansion and function | (70, 71) |
| miR-223 | MEF2C | Suppress accumulation and function | (72–74) |
| miR-142-3p | C/EBPβ/STAT3 | Prevente MDSCs differentiation and immunosuppressive activity |
(75) |
| miR-6991-3p | Galectin 9, STAT3 | Prevente expansion and promote apoptosis | (76) |
| miR-15 family | PD-L1/PD-1 | Inhibit suppressive functions | (77, 78) |
| miR-124 | STAT3 | Reduce the frequencies of MDSCs | (79) |
| LncRNAs regulation | |||
| Olfr29-ps1 | miR-214-3p/MyD88 | Promote differentiation and expansion | (80) |
| RUNXOR | RUNX1, Arg1, iNOS, and STAT3 | Promote development and suppressive functions | (81) |
| MALAT1 | Arg-1 | Inhibit differentiation | (82) |
| HOTAIRM1 | HOXA1-miR124 aix | Promote development and suppressive functions | (83, 84) |
| RNCR3 | miR-185 CHOP | Increase immunosuppressive activity | (85, 86) |
| Pvt1 | Arg-1, ROS | Increase immunosuppressive activity | (87) |
| AK036396 | Ficolin B | Inhibit differentiation | (88) |
THC, 19-tetrahydrocannabinol; DAC, Decitabine; TSA,Trichostatin A; HDAC2, histone deacetylase 2; HDAC11,histone deacetylase 11; STAT3, signal transducer and activator of transcription; IRF8, interferon regulatory factor 8; TNFα, tumor necrosis factor; NOS, nitric oxide synthase; HO, heme oxygenase; C/EBPβ, CCAAT/enhancer-binding protein beta; Runx1, RUNX family transcription factor 1; SOCS3, suppressor of cytokine signaling 3; AMPK, adenosine 5’-monophosphate (AMP)-activated protein kinase; C/EBP, CCAAT/enhancer-binding protein; JAK, janus kinase; PTEN, phosphatase and tensin homologue deleted on chromosome 10; PI3K, phosphatidylinositol 3-kinase; Akt, protein kinase B; SHIP-1, src homology 2-containing jnositol phosphatase-1; HIF-1α, hypoxia-inducible factor-1α; AML1, acute myelocytic leukemia; TRAF, tumor necrosis factor receptor-associated factor; NF-kB, nuclear factor kappa-B; MEF2C, myocyte Enhancer Factor 2C; PD-1, programmed death 1.