MiR-126-5p regulates osteolysis formation and stromal cell proliferation in giant cell tumor through inhibition of PTHrP

Bone. 2014 Sep:66:267-76. doi: 10.1016/j.bone.2014.06.021. Epub 2014 Jun 25.

Abstract

Parathyroid hormone-related protein (PTHrP) has been identified to play a crucial role in osteolysis formation and stromal cell (GCTSC) proliferation in giant cell tumor (GCT). MiR-126-5p is an intronic miRNA identified as tumor suppressor in many tumors, but its role in GCT is poorly understood. We found that miR-126-5p was decreased in GCT and could directly regulate PTHrP expression. Furthermore, miR-126-5p could control osteoclast (OC) differentiation, GCTSC proliferation and osteolysis formation in GCT through negative regulation of PTHrP. Thus, these results suggest that miR-126-5p could directly target PTHrP and have a tumor suppressor function in GCT.

Keywords: Giant cell tumor; Osteoclast differentiation; Osteolysis; PTHrP; miR-126-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Bone Resorption / pathology
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation / genetics
  • Endonucleases / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genetic Engineering
  • Giant Cell Tumors / complications*
  • Giant Cell Tumors / genetics
  • Giant Cell Tumors / pathology*
  • Giant Cells / metabolism
  • Giant Cells / pathology
  • HEK293 Cells
  • Humans
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Osteolysis / etiology*
  • Osteolysis / genetics
  • Osteolysis / pathology*
  • Parathyroid Hormone-Related Protein / antagonists & inhibitors*
  • Parathyroid Hormone-Related Protein / metabolism
  • Stromal Cells / metabolism
  • Stromal Cells / pathology

Substances

  • MIRN126 microRNA, human
  • MicroRNAs
  • Parathyroid Hormone-Related Protein
  • Endonucleases