MicroRNA miR-24 inhibits erythropoiesis by targeting activin type I receptor ALK4

• Published in: Blood Vol. 111; no. 2; pp. 588 - 595
• Main Authors: Wang, Qiang, Huang, Zheng, Xue, Huiling, Jin, Chengcheng, Ju, Xiu-Li, Han, Jing-Dong J., Chen, Ye-Guang
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.01.2008; The Americain Society of Hematology
• Subjects: 3' Untranslated Regions - antagonists & inhibitors; 3' Untranslated Regions - biosynthesis; 3' Untranslated Regions - genetics; Activin Receptors, Type I - antagonists & inhibitors; Activin Receptors, Type I - biosynthesis; Activin Receptors, Type I - genetics; Activins - metabolism; Antigens, CD34; Biological and medical sciences; Cell Differentiation - physiology; Erythropoiesis - physiology; Gene Expression; Gene Expression Regulation - physiology; Genes, Reporter; Hematologic and hematopoietic diseases; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - physiology; Humans; K562 Cells; Medical sciences; MicroRNAs - biosynthesis; MicroRNAs - genetics; Phosphorylation; Smad2 Protein - genetics; Smad2 Protein - metabolism; Erythropoiesis; Gene silencing; RNA interference; Targeting; Hematology; Hematopoiesis; microRNA; Inhibitor; Activin; Biological receptor
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2007-05-092718

MicroRNAs have been suggested to modulate a variety of cellular events. Here we report that miR-24 regulates erythroid differentiation by influencing the expression of human activin type I receptor ALK4 (hALK4). Ectopic expression of miR-24 reduces the mRNA and protein levels of hALK4 by targeting the 3′-untranslated region of hALK4 mRNA and interferes with activin-induced Smad2 phosphorylation and reporter expression. Furthermore, miR-24 represses the activin-mediated accumulation of hemoglobin, an erythroid differentiation marker, in erythroleukemic K562 cells and decreases erythroid colony-forming and burst-forming units of CD34+ hematopoietic progenitor cells. ALK4 expression is inversely correlated with miR-24 expression during the early stages of erythroid differentiation, and the forced expression of miR-24 leads to a delay of activin-induced maturation of hematopoietic progenitor cells in liquid culture. Thus, our findings define a regulation mode of miR-24 on erythropoiesis by impeding ALK4 expression.