| First Author | Fang X | Year | 2018 |
| Journal | Haematologica | Volume | 103 |
| Issue | 3 | Pages | 406-416 |
| PubMed ID | 29269522 | Mgi Jnum | J:317586 |
| Mgi Id | MGI:6851060 | Doi | 10.3324/haematol.2017.177394 |
| Citation | Fang X, et al. (2018) miR-144/451 represses the LKB1/AMPK/mTOR pathway to promote red cell precursor survival during recovery from acute anemia. Haematologica 103(3):406-416 |
| abstractText | The microRNAs miR-144 and -451 are encoded by a bicistronic gene that is strongly induced during red blood cell formation (erythropoiesis). Ablation of the miR-144/451 gene in mice causes mild anemia under baseline conditions. Here we show that miR-144/451(-/-) erythroblasts exhibit increased apoptosis during recovery from acute anemia. Mechanistically, miR-144/451 depletion increases the expression of the miR-451 target mRNA Cab39, which encodes a co-factor for the serine-threonine kinase LKB1. During erythropoietic stress, miR-144/451(-/-) erythroblasts exhibit abnormally increased Cab39 protein, which activates LKB1 and its downstream AMPK/mTOR effector pathway. Suppression of this pathway via drugs or shRNAs enhances survival of the mutant erythroblasts. Thus, miR-144/451 facilitates recovery from acute anemia by repressing Cab39/AMPK/mTOR. Our findings suggest that miR-144/451 is a key protector of erythroblasts during pathological states associated with dramatically increased erythropoietic demand, including acute blood loss and hemolytic anemia. |
