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.

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.

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*

Substances

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