microRNAs (miRs) are highly conserved, non-coding RNAs, that function to regulate gene expression. In mammals this regulation is primarily carried out by repression of translation. miRs play important roles in homeostatic processes such as development, cell proliferation and cell death. Recently the dysregulation of miRs has been linked to cancer initiation and progression, indicating that miRs may play roles as tumor suppressor genes or oncogenes. The role of miRs in apoptosis and migration is not fully understood, however, evidence is mounting that miRs are important in this process. Head and neck cancer, including oral cancer (HNOC) is the sixth most common cancer worldwide accounting for 4% of cancers in men and 2% of cancer in women. Over 90% HNOC are oral squamous cell carcinoma (OSCC). The initiation and progression of OSCC is a complex multistep process that entails a progressive acquisition of genetic and epigenetic alterations. One of the increased proteins in OSCCs identified by our group was the SET protein that functions to regulate gene expression and Akt signaling. Some studies have been performed, in order to detect the miRs expression profile in OSCCs cases, and to determine the characteristics modulate by these miRs. The aims of this study are, identify the miRs regulated by SET in OSCC cell lines using the SET knockdown strategy or SET superexpression in HEK293T, and check these miRs influence on apoptosis, proliferation, invasion and metastasis processes of these cells. To study the SET effects, will also be used an in vivo model based on xenograft and in transgenic animal to increase SET or block its production on cell. The conditioned medium from fibroblast and miofibroblast will be added to OSCC cell culture and the effects in miRNAs will be avaliated. This proposal can increase our knowledgement about cancer progression and suggest a role to SET in this process.
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