Identification of Lethal microRNAs Specific for Head and Neck Cancer

M. van der Plas, S.R. de Kemp, M. de Maaker, W.N. van Wieringen, B. Ylstra, R. Agami, F. Cerisoli, C.R. Leemans, B.J.M. Braakhuis, R.H. Brakenhoff

Research output: Contribution to JournalArticleAcademicpeer-review


Purpose: The prognosis of head and neck squamous cell carcinomas (HNSCC) remains disappointing and the development of novel anti-cancer agents is urgently awaited. We identified by a functional genetic screen microRNAs that are selectively lethal for head and neck cancer cells but not for normal cells. We further investigated the genes targeted by these microRNAs. Experimental Design: A retroviral expression library of human microRNAs was introduced in HNSCC cell lines and normal oropharyngeal keratinocytes to identify tumor-selective lethal microRNAs. Potential downstream gene targets of these microRNAs were identified by gene expression profiling and validated by functional assays. Results: We identified six microRNAs that selectively inhibit proliferation of head and neck cancer cells. By gene expression profiling and 30-untranslated region (UTR) luciferase reporter assays, we showed that the ataxia telangiectasia mutated (ATM) gene is a common target for at least two and likely three of these microRNAs. Specific inhibition of ATM resulted in a similar tumor-specific lethal effect, whereas the phenotype was reverted in rescue experiments. Conclusions: These six microRNAsmight be developed as novel anti-cancer agents and highlight ATMas an interesting novel therapeutic target for head and neck cancer. © 2013 AACR.
Original languageEnglish
Pages (from-to)5647-5657
JournalClinical Cancer Research
Issue number20
Publication statusPublished - 2013


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