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Characterization of microRNA regulatory networks involved in head and neck squamous cell carcinoma by means of microarray and functional studies in cell culture


MicroRNAs (miRNAs) are small noncoding RNA molecules that function as posttranscriptional regulators. They play essential roles in the initiation and progression of human cancer. In this study we aim to determine the possible role of two miRNAs in oral squamous cell carcinoma (OSCC) through functional studies. The miRNAs were selected based on the analysis of miRNA global expression profiling carried out by our group, in which we compared tumor with matched tumor-free surgical margins. In a first approach, we will transfect human oral keratinocytes with miRNA inhibitors and study the impact of the down-regulation of their activity in this cell system. Using a complementary approach, miRNA precursors designed to mimic endogenous mature miRNA will be introduced in the same kind of cells allowing us to assess biological effects via a gain of function experiment. Large-scale effects will be evaluated by means of global gene expression studies using DNA microarrays. The combination of these methods should allow us to draw conclusions on miRNA targets as well as infer mechanisms for their roles in OSCC. We intend to contribute to the understanding of molecular mechanisms underlying OSCC since this comprehension should ultimately lead to the identification of molecular therapeutic targets and prognostic markers. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FLAVIA MAZIERO ANDREGHETTO; MARIA FATIMA GUARIZO KLINGBEIL; RENATA MACHADO SOARES; ROBERTA SITNIK; DÉCIO DOS SANTOS PINTO JUNIOR; MONICA BEATRIZ MATHOR; FABIO DAUMAS NUNES; PATRICIA SEVERINO. Avaliação da expressão de microRNAs em linhagens celulares de carcinoma epidermoide de cabeça e pescoço e em cultura primária de queratinócitos orais. Einstein (São Paulo), v. 9, n. 4, p. 442-448, . (09/04166-5)
SEVERINO, PATRICIA; BRUGGEMANN, HOLGER; ANDREGHETTO, FLAVIA MAZIERO; CAMPS, CARME; GARRIDO KLINGBEIL, MARIA DE FATIMA; DE PEREIRA, WELBERT OLIVEIRA; SOARES, RENATA MACHADO; MOYSES, RAQUEL; WUENSCH-FILHO, VICTOR; MATHOR, MONICA BEATRIZ; et al. MicroRNA expression profile in head and neck cancer: HOX-cluster embedded microRNA-196a and microRNA-10b dysregulation implicated in cell proliferation. BMC CANCER, v. 13, . (09/04166-5)
SEVERINO, PATRICIA; OLIVEIRA, LILIANE SANTANA; TORRES, NATALIA; ANDREGHETTO, FLAVIA MAZIERO; GUARIZO KLINGBEIL, MARIA DE FATIMA; MOYSES, RAQUEL; WUENSCH-FILHO, VICTOR; NUNES, FABIO DAUMAS; MATHOR, MONICA BEATRIZ; PASCHOAL, ALEXANDRE ROSSI; et al. High-throughput sequencing of small RNA transcriptomes reveals critical biological features targeted by microRNAs in cell models used for squamous cell cancer research. BMC Genomics, v. 14, . (10/51168-0, 09/04166-5)

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