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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.

SUBMITTER: Li X 

PROVIDER: S-EPMC3278736 | biostudies-other | 2012 Mar

REPOSITORIES: biostudies-other

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MiR-181 mediates cell differentiation by interrupting the Lin28 and let-7 feedback circuit.

Li X X   Zhang J J   Gao L L   McClellan S S   Finan M A MA   Butler T W TW   Owen L B LB   Piazza G A GA   Xi Yaguang Y  

Cell death and differentiation 20111007 3


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  ...[more]

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