Banca de DEFESA: RENATA OLIVEIRA DE SOUZA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : RENATA OLIVEIRA DE SOUZA
DATE: 29/11/2021
TIME: 09:00
LOCAL: IGM Sala Virtual 5
TITLE:

THE PRIMARY EYEL IN ORAL SCAMOCELLULAR CARCINOMA: PARTICIPATION IN THE REGULATION

OF HEDGEHOG SIGNALING AND CELL PROLIFERATION

KEY WORDS:

Mouth neoplasms, Hedgehog proteins, Cilia

PAGES: 62
BIG AREA: Ciências da Saúde
AREA: Odontologia
SUMMARY:

INTRODUCTION: Oral squamous cell carcinoma (OSCC) is the tumor subtype that most affects oral tissues. The Hedgehog (HH) pathway is an important cascade in embryonic development, which is also associated with tumor development, including the OSCC. The HH pathway occurs canonically in the Primary Cilia (PC), a structure that functions as a cellular sensor and is responsible for housing several signaling pathways. An alteration in the PC function can lead to several problems, including neoplasms. HYPOTHESIS: There is loss of CP in the CECO, which favors the maintenance of cell proliferation and dysregulation of the HH pathway. AIM: To study the ciliogenesis process and the presence of primary cilium in OSCC tissues and cell lines, as well as the relationship between PC, HH molecules and proliferation of cells of this type of tumor. MATERIAL AND METHODS: Tumor cell lines (TC), non-metastatic (CAL27) and metastatic (HSC3), non-tumor cell line (HGK, control) and 22 samples of human tumors (HT) were used. Tumor lines were cultivated in complete DMEM medium supplemented with 10% Fetal Bovine Serum, 1% antibiotics and 8% hydrocortisone; the HGK strain was cultivated in Keratinocyte SFM medium. Cells were analyzed at times 0h and, for TC, also at times 6, 12, 24 and 48h in serum deprivation (synchronization in G0). qPCR was performed at time 0h (TC and HGK) and at times 6, 12 and 24h (TC), as well as for HT samples for gene expression analysis of the HH pathway (PTCH1, SMO, GLI1 and SHH), PC (KIF3A, IFT88, AURKA and BORA) and proliferation (Cyclin D1). For characterization of PC proteins (α-acetylated tubulin), via HH (SMO and GLI1) and proliferation (Ki-67 and profilin), Western Blot (WB) and Immunofluorescence (IF) assays were performed on TC (times 0, 24 and 48h) and HGK (time 0h), as well as Immunohistochemistry in HT. Statistical analysis was performed using the ANOVA test (p<0.05). RESULTS: Assembly and disassembly genes showed lower or similar expression levels in TC when compared to HGK; There was no statistically significant difference between PC assembly and disassembly components, cell proliferation and HH molecules. SHH was not found in the strains studied. The presence of CP in CT was verified, as well as activation of the HH pathway (nuclear GLI1), nuclear and cytoplasmic SMO, as well as cell proliferation (Ki-67 nuclear) greater in TC than in HGK. CONCLUSIONS: CP is present in metastatic and non-metastatic OSCC cells, as well as in human tumors. In these cells and tumors, GLI1 and nuclear SMO were described regardless of the presence of CP, but also in cells that exhibit this organelle. Together, these results indicate activation of the HH pathway, in a canonical and non-canonical manner, in OSCC. Furthermore, cell proliferation occurred independently of CP in cell lines.

BANKING MEMBERS:
Presidente - 3539352 - CLARISSA ARAUJO GURGEL ROCHA
Interno - 3348245 - DANIEL ABENSUR ATHANAZIO
Externo à Instituição - DANIEL PEREIRA BEZERRA
Externo ao Programa - 1227468 - JEAN NUNES DOS SANTOS
Externo à Instituição - THIAGO DE ALMEIDA PEREIRA