miR-199b-5p directly targets PODXL and DDR1 and decreased levels of miR-199b-5p correlate with elevated expressions of PODXL and DDR1 in acute myeloid leukemia

Am J Hematol. 2012 Apr;87(4):442-6. doi: 10.1002/ajh.23129. Epub 2012 Feb 28.


Aberrant expression of Podocalyxin (PODXL), a CD34 orthologue, has been associated with acute myeloid leukemia (AML). Herein, via tissue microarray, we discovered elevated PODXL expression in M2, M4 and M1 FAB-subtype patients. Importantly, various investigations have linked aberrant miRNA expression with AML (1). A miRNA prediction algorithm identified PODXL as a conserved target for miR-199b, a significantly down-regulated miRNA in AML. Further prediction of miR-199b-5p targets identified Discoidin domain receptor 1 (DDR1) as another highly conserved target. For the first time, IHC analyses showed that DDR1 levels were also highly up-regulated in AML and more significantly, were elevated in the same AML cases where PODXL levels were increased. Experimental validation (via-mimics) confirmed that both PODXL and DDR1 are targets of miR-199b-5p. Furthermore, 3’UTR-luciferase assays established that miR-199b-5p targets PODXL and DDR1. Most importantly, we found significant decrease in miR-199b-5p levels in most AML patients with elevated PODXL and DDR1 expressions. Importantly, overexpression of miR-199b-5p in K562 cells caused significant decrease in collagen IV induced migration. Taken together, our studies have identified concurrent increased expression of PODXL and DDR1 in AML and directly connect decreased miR-199b-5p to these novel targets and potential antigomir-mediated therapeutic implications in AML.

Publication types

  • Letter

MeSH terms

  • 3' Untranslated Regions / genetics
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Collagen Type IV
  • Discoidin Domain Receptor 1
  • Gene Expression Regulation, Leukemic
  • Gene Silencing
  • Genetic Vectors / pharmacology
  • Humans
  • K562 Cells
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myelomonocytic, Acute / genetics*
  • Leukemia, Myelomonocytic, Acute / pathology
  • MicroRNAs / genetics*
  • Molecular Targeted Therapy
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Receptor Protein-Tyrosine Kinases / biosynthesis
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Sialoglycoproteins / biosynthesis
  • Sialoglycoproteins / genetics*
  • Transfection
  • Up-Regulation


  • 3' Untranslated Regions
  • Collagen Type IV
  • MicroRNAs
  • Neoplasm Proteins
  • Sialoglycoproteins
  • mirn199 microRNA, human
  • podocalyxin
  • DDR1 protein, human
  • Discoidin Domain Receptor 1
  • Receptor Protein-Tyrosine Kinases