Profile analysis of SET-associated miRNAs and its effects on proliferation, invasion and migration in an oral squamous cell carcinoma model - in vivo and in vitro

• Grant number: 10/18544-9
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): March 01, 2011
• Effective date (End): February 28, 2014
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Andréia Machado Leopoldino
• Grantee: Lays Martin Sobral
• Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

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.

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)

SOBRAL, LAYS M.; COLETTA, RICARDO D.; ALBERICI, LUCIANE C.; CURTI, CARLOS; LEOPOLDINO, ANDREIA M. SET/I2PP2A overexpression induces phenotypic, molecular, and metabolic alterations in an oral keratinocyte cell line. FEBS Journal, v. 284, n. 17, p. 2774-2785, SEP 2017. Web of Science Citations: 4.

SOBRAL, LAYS M.; SOUSA, LUCAS O.; COLETTA, RICARDO D.; CABRAL, HAMILTON; GREENE, LEWIS J.; TAJARA, ELOIZA H.; GUTKIND, J. SILVIO; CURTI, CARLOS; LEOPOLDINO, ANDREIA M. Stable SET knockdown in head and neck squamous cell carcinoma promotes cell invasion and the mesenchymal-like phenotype in vitro, as well as necrosis, cisplatin sensitivity and lymph node metastasis in xenograft tumor models. Molecular Cancer, v. 13, FEB 20 2014. Web of Science Citations: 29.