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Decrease of miR-146a is associated with the aggressiveness of human oral squamous cell carcinoma.

Zonggao Shi1, Jeffrey J Johnson1, Rong Jiang2

  • 1Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46617, United States; Department of Chemistry and Biochemistry, University of Notre Dame, South Bend, IN 46617, United States.

Archives of Oral Biology
|July 11, 2015
PubMed
Summary

Loss of microRNA-146a (miR-146a) expression correlates with aggressive oral squamous cell carcinoma (OSCC). Restoring miR-146a reduced tumor growth and metastasis, identifying it as a potential therapeutic target.

Keywords:
MetastasisMicroRNAOral cancermiR-146a

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Oral squamous cell carcinoma (OSCC) is a significant global health concern.
  • Understanding the molecular mechanisms driving OSCC progression is crucial for developing effective treatments.

Purpose of the Study:

  • To identify microRNAs (miRNAs) involved in the progression of oral squamous cell carcinoma (OSCC).
  • To investigate the role of miR-146a in OSCC aggressiveness and metastasis.

Main Methods:

  • Comparative microRNA expression profiling of OSCC cell lines with differential tumor aggressiveness.
  • Validation of miR-146a expression loss in human high-grade OSCC tumors using fluorescence in situ hybridization (FISH).
  • Functional studies involving restoration of miR-146a in OSCC cells to assess effects on invasion, tumor growth, and metastasis.

Main Results:

  • A panel of 28 miRNAs showed significant alterations, with miR-146a exhibiting the most substantial decrease (-4.6-fold).
  • Loss of miR-146a expression was confirmed in high-grade human OSCC tissues compared to normal oral mucosa.
  • Restoration of miR-146a suppressed in vitro invasion, inhibited in vivo tumor growth, and reduced lung metastasis incidence.
  • The transcription factor Sox2 was identified as a putative target of miR-146a.

Conclusions:

  • Loss or decreased expression of miR-146a is a novel characteristic associated with increased aggressiveness in oral squamous cell carcinoma.
  • miR-146a functions as a tumor suppressor in OSCC, potentially through targeting Sox2.
  • Targeting miR-146a represents a potential therapeutic strategy for managing aggressive OSCC.