The active component of Ginseng, Ginsenoside Rb1, improves erythropoiesis in models of Diamond Blackfan Anemia by targeting Nemo-like Kinase.
The Journal of biological chemistry
Nemo-like kinase (NLK) is a member of the MAPK family of kinases and shares a highly conserved kinase domain with other MAPK family members. The activation of NLK contributes to the pathogenesis of Diamond Blackfan Anemia (DBA), reducing c-myb expression and mTOR activity, and is therefore a potential therapeutic target. Unlike other anemia's, the hematopoietic effects of DBA are largely restricted to the erythroid lineage. Mutations in ribosomal genes induces ribosomal insufficiency and reduced protein translation, dramatically impacting early erythropoiesis in the bone marrow of DBA patients. We sought to identify compounds that suppress NLK and increases erythropoiesis in ribosomal insufficiency. We report that the active component of ginseng, ginsenoside Rb1, suppresses NLK expression and improves erythropoiesis in in vitro models of Diamond Blackfan Anemia. Ginsenoside Rb1-mediated suppression of NLK occurs through the upregulation of miR-208, which binds to the 3'-UTR of NLK mRNA and targets it for degradation. We also compare ginsenoside Rb1-mediated upregulation of miR-208 with metformin-mediated upregulation of miR-26. We conclude that targeting NLK expression through miRNA binding of the unique 3'-UTR is a viable alternative to the challenges of developing small molecule inhibitors to target the highly conserved kinase domain of this specific kinase.
View details for DOI 10.1016/j.jbc.2021.100988
View details for PubMedID 34298020