| First Author | Xu L | Year | 2020 |
| Journal | FASEB J | Volume | 34 |
| Issue | 10 | Pages | 13194-13210 |
| PubMed ID | 33319407 | Mgi Jnum | J:330755 |
| Mgi Id | MGI:6714586 | Doi | 10.1096/fj.202000941R |
| Citation | Xu L, et al. (2020) miR-144/451 inhibits c-Myc to promote erythroid differentiation. FASEB J 34(10):13194-13210 |
| abstractText | Ablation of miR-144/451 disrupts homeostasis of erythropoiesis. Myc, a protooncogenic protein, is essential for erythroblast proliferation but commits rapid downregulation during erythroid maturation. How erythroblasts orchestrate maturation processes through coding and non-coding genes is largely unknown. In this study, we use miR-144/451 knockout mice as in vivo model, G1E, MEL erythroblast lines and erythroblasts from fresh mouse fetal livers as in vitro systems to demonstrate that targeted depletion of miR-144/451 blocks erythroid nuclear condensation and enucleation. This is due, at least in part, to the continued high expression of Myc in erythroblasts when miR-144/451 is absent. Specifically, miR-144/451 directly inhibits Myc in erythroblasts. Loss of miR-144/451 locus derepresses, and thus, increases the expression of Myc. Sustained high levels of Myc in miR-144/451-depleted erythroblasts blocks erythroid differentiation. Moreover, Myc reversely regulates the expression of miR-144/451, forming a positive miR-144/451-Myc feedback to ensure the complete shutoff of Myc during erythropoiesis. Given that erythroid-specific transcription factor GATA1 activates miR-144/451 and inactivates Myc, our findings indicate that GATA1-miR-144/451-Myc network safeguards normal erythroid differentiation. Our findings also demonstrate that disruption of the miR-144/451-Myc crosstalk causes anemia, suggesting that miR-144/451 might be a potential therapeutic target in red cell diseases. |
