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Identification of lethal microRNAs specific for head and neck cancer

Marlon Lindenbergh-van der Plas1, Sanne R Martens-de Kemp, Michiel de Maaker

  • 1Authors' Affiliations: Departments of Otolaryngology/Head-Neck Surgery, Epidemiology and Biostatistics, and Pathology, VU University Medical Center; Department of Mathematics, VU University; Division of Gene Regulation, The Netherlands Cancer Institute, Amsterdam; and InteRNA Technologies BV, Utrecht, The Netherlands.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|August 15, 2013
PubMed
Abstract

Insights

Researchers discovered six microRNAs that kill head and neck cancer cells but not normal cells. These microRNAs target the ATM gene, offering a potential new therapy for head and neck squamous cell carcinomas.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Head and neck squamous cell carcinomas (HNSCC) have a poor prognosis, necessitating new therapeutic strategies.
  • MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have roles in cancer development.
  • Identifying tumor-specific lethal miRNAs could lead to novel anti-cancer treatments.

Purpose of the Study:

  • To identify microRNAs that selectively kill HNSCC cells.
  • To investigate the genes targeted by these tumor-selective lethal miRNAs.
  • To evaluate the therapeutic potential of these miRNAs and their targets in HNSCC.

Main Methods:

  • Functional genetic screening using a retroviral expression library of human miRNAs in HNSCC cell lines and normal keratinocytes.
  • Gene expression profiling to identify downstream targets of candidate miRNAs.
  • 3'-untranslated region (UTR) luciferase reporter assays and functional assays to validate miRNA targets.

Main Results:

  • Six microRNAs were identified that selectively inhibit HNSCC cell proliferation.
  • The ataxia telangiectasia mutated (ATM) gene was identified as a common target for multiple identified miRNAs.
  • Inhibition of ATM mimicked the tumor-specific lethal effect of the miRNAs, and rescue experiments confirmed this finding.

Conclusions:

  • The identified six microRNAs show potential as novel anti-cancer agents for HNSCC.
  • The ataxia telangiectasia mutated (ATM) gene represents a promising therapeutic target for head and neck cancer treatment.

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