| First Author | Hu M | Year | 2021 |
| Journal | Haematologica | Volume | 106 |
| Issue | 2 | Pages | 412-423 |
| PubMed ID | 31974197 | Mgi Jnum | J:331241 |
| Mgi Id | MGI:6823248 | Doi | 10.3324/haematol.2019.236927 |
| Citation | Hu M, et al. (2021) MicroRNA-21 maintains hematopoietic stem cell homeostasis through sustaining the NF-kappaB signaling pathway in mice. Haematologica 106(2):412-423 |
| abstractText | Long-term hematopoietic output is dependent on hematopoietic stem cell (HSC) homeostasis which is maintained by a complex molecular network. Among these, microRNAs play crucial roles, while the underlying molecular basis has not been fully elucidated. Here, we show that miR-21 is enriched in murine HSCs, and mice with conditional knockout of miR-21 exhibit an obvious perturbation in normal hematopoiesis. Moreover, significant loss of HSC quiescence and long-term reconstituting ability are observed in the absence of miR-21. Further studies reveal that miR-21 deficiency markedly decreases the NF-kappaB pathway, accompanied by increased expression of PDCD4, a direct target of miR-21, in HSCs. Interestingly, overexpression of PDCD4 in wild-type HSCs generates similar phenotypes as those of miR-21-deficient HSCs. More importantly, knockdown of PDCD4 can significantly rescue the attenuation of NF-kappaB activity, thereby improving the defects in miR-21-null HSCs. On the other hand, we find that miR-21 is capable of preventing HSCs from ionizing radiation-induced DNA damage via activation of the NF-kappaB pathway. Collectively, our data demonstrate that miR-21 is involved in maintaining HSC homeostasis and function, at least in part, by regulating the PDCD4-mediated NF-kappaB pathway and provide a new insight into the radioprotection of HSCs. |
