MicroRNA and protein profiles in invasive versus non-invasive oral tongue squamous cell carcinoma cells in vitro |
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Authors: | Johanna Korvala Kowan Jee Emmi Porkola Alhadi Almangush Neda Mosakhani Carolina Bitu Nilva K Cervigne Flávia S Zandonadi Gabriela V Meirelles Adriana Franco Paes Leme Ricardo D Coletta Ilmo Leivo Tuula Salo |
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Institution: | 1. Cancer and Translational Medicine Research Unit, University of Oulu, The Medical Research Center Oulu, Oulu University Hospital, Aapistie 5A, 90014 Oulu, Finland;2. Department of Pathology, University of Turku, Turku University Hospital, Turku, Finland;3. Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland;4. Department of Pathology, HUSLAB, Helsinki, Finland;5. Department of Oral Diagnosis, School of Dentistry, University of Campinas (UNICAMP), Av. Limeira, 901 – Bairro Areião, CEP: 13414-903 Piracicaba, São Paulo, Brazil;6. Department of Clinical and Pathology, Faculty of Medicine of Jundiai - FMJ, Jundiai, SP, Brazil;7. Laboratório Nacional de Biociências, LNBio, CNPEM, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas/SP, P.O.Box 6192, CEP 13083-970 Campinas, São Paulo, Brazil;8. Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland |
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Abstract: | Complex molecular pathways regulate cancer invasion. This study overviewed proteins and microRNAs (miRNAs) involved in oral tongue squamous cell carcinoma (OTSCC) invasion. The human highly aggressive OTSCC cell line HSC-3 was examined in a 3D organotypic human leiomyoma model. Non-invasive and invasive cells were laser-captured and protein expression was analyzed using mass spectrometry-based proteomics and miRNA expression by microarray. In functional studies the 3D invasion assay was replicated after silencing candidate miRNAs, miR-498 and miR-940, in invasive OTSCC cell lines (HSC-3 and SCC-15). Cell migration, proliferation and viability were also studied in the silenced cells. In HSC-3 cells, 67 proteins and 53 miRNAs showed significant fold-changes between non-invasive vs. invasive cells. Pathway enrichment analyses allocated “Focal adhesion” and “ECM-receptor interaction” as most important for invasion. Significantly, in HSC-3 cells, miR-498 silencing decreased the invasion area and miR-940 silencing reduced invasion area and depth. Viability, proliferation and migration weren’t significantly affected. In SCC-15 cells, down-regulation of miR-498 significantly reduced invasion and migration. This study shows HSC-3 specific miRNA and protein expression in invasion, and suggests that miR-498 and miR-940 affect invasion in vitro, the process being more influenced by mir-940 silencing in aggressive HSC-3 cells than in the less invasive SCC-15. |
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