MiR-542-5p is a negative prognostic factor and promotes osteosarcoma tumorigenesis by targeting HUWE1

Oncotarget. 2015 Dec 15;6(40):42761-72. doi: 10.18632/oncotarget.6199.

Abstract

Recent evidence has demonstrated that microRNAs (miRNAs) are involved in the proliferation and metastasis of osteosarcoma. Using miRNA microarray and functional screening methods to compare miRNA expression profiles in osteosarcoma cell lines treated with Trichostatin A (TSA), overexpression of miR-542-5p was determined to be involved in the proliferation of osteosarcoma. We used isobaric tags for relative and absolute quantitation (iTRAQ) and nanoscale liquid chromatography-mass spectrometry (NanoLC-MS/MS) to identify differentially expressed proteins in MNNG/HOS and U2OS osteosarcoma cell lines transfected with miR-542-5p; in both cell lines, seven proteins were downregulated, and nine were upregulated. HUWE1 was found to be a direct target of miR-542-5p in both osteosarcoma cell lines, and was negatively correlated with miR-542-5p levels in human osteosarcoma tissues. Moreover, the expression of miR-542-5p was upregulated in human osteosarcoma tissue compared with non-tumor adjacent tissue. Kaplan-Meier analysis revealed that overexpression of miR-542-5p predicted poor prognosis for osteosarcoma patients. Taken together, our results indicated that miR-542-5p plays a critical role in the proliferation of osteosarcoma and targets HUWE1.

Keywords: HUWE1; miR-542-5p; osteosarcoma; proliferation; proteomics.

MeSH terms

  • Animals
  • Blotting, Western
  • Bone Neoplasms / genetics
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology*
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Chromatography, Liquid
  • Gene Expression Regulation, Neoplastic / genetics*
  • Heterografts
  • Humans
  • Kaplan-Meier Estimate
  • Mass Spectrometry
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Osteosarcoma / genetics
  • Osteosarcoma / mortality
  • Osteosarcoma / pathology*
  • Prognosis
  • Real-Time Polymerase Chain Reaction
  • Transfection
  • Tumor Suppressor Proteins
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • MIRN542 microRNA, human
  • MicroRNAs
  • Tumor Suppressor Proteins
  • HUWE1 protein, human
  • Ubiquitin-Protein Ligases