MicroRNA-125b regulates proliferation and radioresistance of oral squamous cell carcinoma

Br J Cancer. 2013 May 14;108(9):1817-21. doi: 10.1038/bjc.2013.175. Epub 2013 Apr 16.

Abstract

Background: MicroRNAs (miRNAs) are involved in essential biological activities, and have been reported to exhibit differential expression profiles in various cancers. Our previous study demonstrated that intercellular adhesion molecule-2 (ICAM2) inhibition induces radiosensitisation in oral squamous cell carcinoma (OSCC) cells. Thus, we hypothesised that certain miRNAs play crucial roles in radioresistance in OSCC by regulating ICAM2 expression.

Methods: Because predicted target gene analyses revealed that microRNA-125b (miR-125b) potentially regulates ICAM2 mRNA expression, we examined the association between miR-125b and radioresistance. The expression of miR-125b was investigated by real-time quantitative reverse transcriptase-PCR. For a functional analysis, miR-125b was transfected to OSCC-derived cells.

Results: A downregulated expression of miR-125b was found in OSCC-derived cell lines and OSCC samples. The miR-125b-transfected cells showed a decreased proliferation rate, enhanced radiosensitivity to X-ray irradiation and diminished ICAM2 mRNA expression. Moreover, miR-125b expression correlated with OSCC tumour staging and survival.

Conclusion: These findings suggested that the downregulated miR-125b expression was associated with proliferation and radioresistance mechanisms, probably through ICAM2 signalling. Thus, controlling the expression or activity of miR-125b might contribute to suppressing proliferation and overcoming radioresistance in OSCC.

MeSH terms

  • Antigens, CD / biosynthesis
  • Antigens, CD / metabolism*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / radiotherapy*
  • Cell Adhesion Molecules / biosynthesis
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / radiotherapy*
  • Prognosis
  • RNA, Messenger / biosynthesis
  • Radiation Tolerance / genetics*
  • Signal Transduction
  • Transfection
  • X-Rays

Substances

  • Antigens, CD
  • Cell Adhesion Molecules
  • ICAM2 protein, human
  • MIRN125 microRNA, human
  • MicroRNAs
  • RNA, Messenger