Dysregulation of Mir-196b in Head and Neck Cancers Leads to Pleiotropic Effects in the Tumor Cells and Surrounding Stromal Fibroblasts

The miR-196 family members have been found dysregulated in different cancers. Therefore, they have been proposed as promising biomarkers and therapeutic targets. This study is the first to investigate the role of miR-196b in the development and progression of head and neck squamous cell carcinomas (...

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Published in:	Scientific reports 2017-12, Vol.7 (1), p.17785-11, Article 17785
Main Authors:	Álvarez-Teijeiro, Saúl, Menéndez, Sofía T, Villaronga, M Ángeles, Rodrigo, Juan P, Manterola, Lorea, de Villalaín, Lucas, de Vicente, Juan C, Alonso-Durán, Laura, Fernández, M Pilar, Lawrie, Charles H, García-Pedrero, Juana M
Format:	Article
Language:	eng
Subjects:	Adult Aged Cancer Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - pathology Cell Line, Tumor Cell migration Cell proliferation Cell Proliferation - genetics Data processing Female Fibroblasts Fibroblasts - pathology Gene Expression Regulation, Neoplastic - genetics Head & neck cancer Head and neck Head and neck carcinoma Head and Neck Neoplasms - genetics Head and Neck Neoplasms - pathology Humans Lymphocytes B Male MicroRNAs - genetics Middle Aged Saliva Squamous cell carcinoma Squamous Cell Carcinoma of Head and Neck - genetics Squamous Cell Carcinoma of Head and Neck - pathology Studies Transfection Tumor cell lines Tumor cells Tumor Microenvironment - genetics Tumorigenesis
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Summary:	The miR-196 family members have been found dysregulated in different cancers. Therefore, they have been proposed as promising biomarkers and therapeutic targets. This study is the first to investigate the role of miR-196b in the development and progression of head and neck squamous cell carcinomas (HNSCC), and also the impact on the surrounding tumor microenvironment. Increased miR-196b levels were detected in 95% of primary tumors and precancerous lesions, although no significant differences were observed between non-progressing versus progressing dysplasias. Furthermore, increased levels of both miR-196a and miR-196b were successfully detected in saliva samples from HNSCC patients. The functional consequences of altered miR-196 expression were investigated in both HNSCC cell lines and cancer-associated fibroblasts (CAFs) by transfection with specific pre-miR precursors. Results showed that both miR-196a and miR-196b elicit cell-specific responses in target genes and downstream regulatory pathways, and have a distinctive impact on cell proliferation, migration and invasion. These data reveal the early occurrence and prevalence of miR-196b dysregulation in HNSCC tumorigenesis, suggesting its utility for early diagnosis and/or disease surveillance and also as a non-invasive biomarker in saliva. The pleiotropic effects of miR-196a/b in HNSCC cell subpopulations and surrounding CAFs may complicate a possible therapeutic application.
ISSN:	2045-2322 2045-2322