title: MiR-181 mediates cell differentiation by interrupting the Lin28 and let-7 feedback circuit.
abstract: MicroRNAs (miRNAs) have attracted attention because of their key regulatory functions in many biological events, including differentiation and tumorigenesis. Recent studies have reported the existence of a reciprocal regulatory loop between the family of let-7 miRNAs and an RNA-binding protein, Lin28, both of which have been documented for their important roles during cell differentiation. Hence, using bipotent K562 human leukemia cells and human CD34+ hematopoietic progenitor cells as research models, we demonstrate that let-7 and Lin28 have contrary roles in megakaryocytic (MK) differentiation with a dynamic balance; expression of miR-181 is capable of effectively repressing Lin28 expression, disrupting the Lin28-let-7 reciprocal regulatory loop, upregulating let-7, and eventually promoting MK differentiation. However, miR-181 lacks a significant effect on hemin-induced erythrocyte differentiation. These results demonstrate that miR-181 can function as a 'molecular switch' during hematopoietic lineage progression specific to MK differentiation, thus providing insight into future development of miRNA-oriented therapeutics.
authors: 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, China.
authors: X
authors: X
authors: Li
authors: J
authors: J
authors: Zhang
authors: L
authors: L
authors: Gao
authors: S
authors: S
authors: McClellan
authors: M A
authors: MA
authors: Finan
authors: T W
authors: TW
authors: Butler
authors: L B
authors: LB
authors: Owen
authors: G A
authors: GA
authors: Piazza
authors: Yaguang
authors: Y
authors: Xi
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C000715187:Lin28A protein, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C487931:mirnlet7 microRNA, human