Dysregulation of Mir-196b in Head and Neck Cancers Leads to Pleiotropic Effects in the Tumor Cells and Surrounding Stromal Fibroblasts
Autor: | Saúl Álvarez-Teijeiro, Juana M. García-Pedrero, Charles H. Lawrie, M. Pilar Fernandez, Lucas de Villalaín, M. Ángeles Villaronga, Laura Alonso-Durán, Sofía T. Menéndez, Juan Carlos de Vicente, Lorea Manterola, Juan P. Rodrigo |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
Adult
Male 0301 basic medicine Cell lcsh:Medicine medicine.disease_cause Article 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Tumor Microenvironment Carcinoma Humans Medicine lcsh:Science Aged Cell Proliferation Regulation of gene expression Tumor microenvironment Multidisciplinary Squamous Cell Carcinoma of Head and Neck business.industry Cell growth lcsh:R Transfection Fibroblasts Middle Aged medicine.disease Gene Expression Regulation Neoplastic MicroRNAs stomatognathic diseases 030104 developmental biology medicine.anatomical_structure Head and Neck Neoplasms 030220 oncology & carcinogenesis Carcinoma Squamous Cell Cancer research Biomarker (medicine) Female lcsh:Q business Carcinogenesis |
Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) Scientific Reports Scopus RUO. Repositorio Institucional de la Universidad de Oviedo instname |
ISSN: | 2045-2322 |
DOI: | 10.1038/s41598-017-18138-8 |
Popis: | 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. |
Databáze: | OpenAIRE |
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