MicroRNA-223 reversibly regulates erythroid and megakaryocytic differentiation of K562 cells.
MicroRNAs (miRNAs) are thought to modulate a variety of cellular events. Several studies have revealed the functions of miR-223 in granulopoiesis. Here we analysed miR-223 expression in various human tissues, blood and leukaemia cells, and focused on its role in K562 erythroid and megakaryocytic differentiation. MiR-223 was detected not only in granulocytes but also in erythroid cells. In K562 cells, expression of miR-223 was down-regulated during haemin-induced erythroid differentiation but up-regulated during phorbol myristate acetate (PMA)-induced megakaryocytic differentiation. The overexpression of miR-223 resulted in significant decrease of gamma-globin mRNA and the fraction of benzidine-positive cells in K562 cells, suggesting a suppressive effect of miR-223 on erythroid differentiation. Peaks corresponding to 4N cells in stable transfectants overexpressing miR-223 were higher than that in control K562 cells during megakaryocytic differentiation, indicating that miR-223 increases megakaryocytic differentiation. The expression of LIM domain only 2 (LMO2) reporter was suppressed in NIH-3T3 when the expression of miR-223 was enforced by both the luciferase and fluorescence system. Furthermore, LMO2 mRNA and protein levels were significantly decreased in stable K562 transfectants overexpressing miR-223. These results indicate that LMO2 is a direct target of miR-223. Thus, our results suggest that miR-223 reversibly regulates erythroid and megakaryocytic differentiation of K562 cells via down-modulation of LMO2.
Yuan
Jin-Yun
JY
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing, People's Republic of China.
Wang
Fang
F
Yu
Jia
J
Yang
Gui-Hua
GH
Liu
Xiao-Ling
XL
Zhang
Jun-Wu
JW
D048868:Adaptor Proteins, Signal Transducing; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D041905:Erythroid Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects / Q000235:genetics; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D060588:LIM Domain Proteins; D008533:Megakaryocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008667:Metalloproteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D006427:Hemin; D060588:LIM Domain Proteins; D008667:Metalloproteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate; C085117:LMO2 protein, human; C525067:MIR223, human