MicroRNA expression and functional profiles of osteosarcoma

Oncology. 2014;86(2):94-103. doi: 10.1159/000357408. Epub 2014 Jan 18.

Abstract

Objective: Osteosarcoma (OS) is the most frequent primary malignant bone tumor in children and young adults. Although the introduction of combined neoadjuvant chemotherapy has significantly prolonged survival, the outcome for OS patients showing a poor response to chemotherapy is still unfavorable. In order to develop new therapeutic approaches, elucidation of the entire molecular pathway regulating OS cell proliferation would be desirable.

Methods: MicroRNA (miRNA) are highly conserved noncoding RNA that play important roles in the development and progression of various other cancers. Using miRNA microarrays capable of detecting a known number of 933 miRNA, 108 miRNA were found to be commonly expressed in 24 samples of OS tissue and subjected to a cell proliferation assay.

Results: We found that inhibition of 5 let-7 family miRNA (hsa-let-7a, b, f, g and i) significantly suppressed the proliferation of OS cells. Using a quantitative shotgun proteomics approach, we also found that the let-7 family miRNA regulated the expression of vimentin and serpin H1 proteins.

Conclusions: Our present results indicate the involvement of let-7 family miRNA in regulation of the cell proliferation as well as epithelial-mesenchymal transition of OS. Thus, let-7 family miRNA may potentially provide novel targets for the development of therapeutic strategies against OS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Child
  • Female
  • Gene Expression Regulation, Neoplastic
  • HSP47 Heat-Shock Proteins / chemistry
  • HSP47 Heat-Shock Proteins / genetics
  • HSP47 Heat-Shock Proteins / metabolism
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism*
  • RNA Interference
  • Transcriptome
  • Vimentin / chemistry
  • Vimentin / genetics
  • Vimentin / metabolism
  • Young Adult

Substances

  • HSP47 Heat-Shock Proteins
  • MicroRNAs
  • Vimentin
  • mirnlet7 microRNA, human