Circulating small non coding RNA signature in head and neck squamous cell carcinoma
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Berta Victoria Martinez1,*, Joseph M. Dhahbi2,*, Yury O. Nunez Lopez3, Katarzyna Lamperska4, Paweł Golusinski5,6, Lukasz Luczewski6, Tomasz Kolenda4,7, Hani Atamna8, Stephen R. Spindler2, Wojciech Golusinski6 and Michal M. Masternak1,6
1 University of Central Florida, Burnett School of Biomedical Sciences, College of Medicine Orlando, FL, USA
2 Department of Biochemistry, University of California at Riverside, Riverside, CA, USA
3 Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL, USA
4 Deptartment of Cancer Genetics, Greater Poland Cancer Centre, Poznan, Poland
5 Department of Biology and Environmental Studies, Poznan University of Medical Sciences, Poznan, Poland
6 Department of Head and Neck Surgery, Greater Poland Cancer Centre, Poznan University of Medical Sciences, Poznan, Poland
7 Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warszawa, Poland
8 Department of Medical Education, California Northstate University, Elk Grove, CA, USA
* These authors have contributed equally to this paper
Michal M. Masternak, email:
Joseph M. Dhahbi, email:
Keywords: head and neck cancer, next-generation sequencing, circulating small RNAs, microRNAs, tRNA halves
Received: March 18, 2015 Accepted: May 13, 2015 Published: May 25, 2015
The Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common human cancer, causing 350,000 individuals die worldwide each year. The overall prognosis in HNSCC patients has not significantly changed for the last decade. Complete understanding of the molecular mechanisms in HNSCC carcinogenesis could allow an earlier diagnosis and the use of more specific and effective therapies. In the present study we used deep sequencing to characterize small non-coding RNAs (sncRNAs) in serum from HNSCC patients and healthy donors. We identified, for the first time, a multi-marker signature of 3 major classes of circulating sncRNAs in HNSCC, revealing the presence of circulating novel and known miRNAs, and tRNA- and YRNA-derived small RNAs that were significantly deregulated in the sera of HNSCC patients compared to healthy controls. By implementing a triple-filtering approach we identified a subset of highly biologically relevant miRNA-mRNA interactions and we demonstrated that the same genes/pathways affected by somatic mutations in cancer are affected by changes in the abundance of miRNAs. Therefore, one important conclusion from our work is that during cancer development, there seems to be a convergence of oncogenic processes driven by somatic mutations and/or miRNA regulation affecting key cellular pathways.
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