Wang Qiang, Huang Zheng, Xue Huiling, Jin Chengcheng, Ju Xiu-Li, Han Jing-Dong J, Chen Ye-Guang
State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, China.
Blood. 2008 Jan 15;111(2):588-95. doi: 10.1182/blood-2007-05-092718. Epub 2007 Sep 28.
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.
已有研究表明，微小RNA可调节多种细胞事件。在此我们报告，miR-24通过影响人激活素I型受体ALK4（hALK4）的表达来调控红系分化。miR-24的异位表达通过靶向hALK4 mRNA的3'-非翻译区降低hALK4的mRNA和蛋白水平，并干扰激活素诱导的Smad2磷酸化及报告基因表达。此外，miR-24抑制红白血病K562细胞中激活素介导的血红蛋白积累（一种红系分化标志物），并减少CD34+造血祖细胞的红系集落形成单位和爆式集落形成单位。在红系分化早期，ALK4表达与miR-24表达呈负相关，miR-24的强制表达导致液体培养中激活素诱导的造血祖细胞成熟延迟。因此，我们的研究结果确定了miR-24通过阻碍ALK4表达对红细胞生成的调控模式。
