MiR-886-3p down regulates CXCL12 (SDF1) expression in human marrow stromal cells

Manoj M Pillai1, Xiaodong Yang, Ilango Balakrishnan

  • 1Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America. Manoj.Pillai@UCDenver.edu

Plos One
|December 24, 2010
PubMed

Insights

MicroRNA-886-3p significantly down-regulates Stromal Derived Factor 1 (SDF1 or CXCL12) expression in stromal cells. This suggests microRNAs play a role in regulating CXCL12, crucial for hematopoietic stem cell homing.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Hematology

Background:

  • Stromal Derived Factor 1 (SDF1 or CXCL12) is a key chemokine regulating cell migration, including hematopoietic stem cell (HSC) homing.
  • Stromal cell lines exhibit functional differences and varying CXCL12 expression levels (CXCL12+ vs. CXCL12-).

Purpose of the Study:

  • To investigate the role of microRNAs in regulating CXCL12 expression in stromal cells.
  • To identify specific microRNAs involved in modulating CXCL12 levels and function.

Main Methods:

  • Comparative analysis of miRNA expression profiles in CXCL12+ and CXCL12- stromal cell lines.
  • Transfection of miR-886-3p into stromal cells to assess its effect on CXCL12 expression and function.
  • Identification of the target site of miR-886-3p within the CXCL12 mRNA 3' untranslated region (UTR).

Main Results:

  • CXCL12- stromal cells showed significantly higher expression (>40 fold) of miR-886-3p compared to CXCL12+ cells.
  • Transfection of miR-886-3p into CXCL12+ stromal cells led to an 85% down-regulation of CXCL12 expression.
  • miR-886-3p transfection resulted in the loss of CXCL12-directed chemotaxis and reduced CXCL12 expression in primary stromal cultures.
  • miR-886-3p was confirmed to specifically target the 3' UTR of CXCL12 mRNA.

Conclusions:

  • MicroRNA-886-3p plays a significant role in down-regulating CXCL12 expression.
  • These findings highlight a novel mechanism by which microRNAs modulate CXCL12, impacting hematopoietic regulation.
  • This study identifies a potential regulatory pathway for controlling CXCL12-mediated cellular processes.