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

Cell Death Differ. 2012 Mar;19(3):378-86. doi: 10.1038/cdd.2011.127. Epub 2011 Oct 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / physiology*
  • Gene Expression Regulation / physiology
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • K562 Cells
  • Megakaryocytes / cytology
  • Megakaryocytes / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*


  • LIN-28 protein, human
  • MIrn181 microRNA, human
  • MicroRNAs
  • RNA-Binding Proteins
  • mirnlet7 microRNA, human