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Mémoire de Maîtrise
DOI
https://doi.org/10.11606/D.42.2010.tde-27092010-152352
Document
Auteur
Nom complet
Cesar Seigi Fuziwara
Unité de l'USP
Domain de Connaissance
Date de Soutenance
Editeur
São Paulo, 2010
Directeur
Jury
Kimura, Edna Teruko (Président)
Chaves, Maria Luiza Morais Barreto de
Rubio, Ileana Gabriela Sanchez de
Titre en portugais
Influência do MicroRNA let-7 e miR-17-92 como oncomiRs no câncer.
Mots-clés en portugais
Glândula tireóide
Let-7
MicroRNA
miR-17-92
Neoplasias da tireóide
Proliferação RET/PTC
Resumé en portugais
No câncer, alterações em microRNAs (miRNAs), pequenos RNAs que regulam a tradução protéica, exerce efeito oncogênico (oncomiR). Os oncomiRs regulam genes chave para a proliferação celular e apoptose, sendo importantes para a biologia do câncer. O carcinoma papilífero de tiróide apresenta alterações genéticas alinhadas na via MAPK (RET>RAS>BRAF>ERK). Observamos que a indução do oncogene RET/PTC diminui a expressão de let-7 em células foliculares tiroidianas. Na linhagem TPC-1 (com RET/PTC-1), a introdução de let-7 diminui a proliferação celular e a fosforilaçãode ERK, indicando papel de gene supressor tumoral. No carcinoma anaplásico, avaliamos o papel da introdução do cluster miR-17-92 na linhagem ARO. Observamos que in vitro miR-17-92 atua de forma oncogênica aumentando proliferação e viabilidade celular de ARO. No entanto, estas células apresentam diminuição no crescimento em soft-agar. No xenotransplante, os tumores de ARO-miR-17-92 apresentam menor volume e expressam MMP-9 de forma reduzida, indicando também um papel de gene supressor tumoral para o cluster.
Titre en anglais
Influence of MicroRNA let-7 and miR-17-92 as oncomiRs in cancer.
Mots-clés en anglais
Let-7
MicroRNA
miR-17-92
Proliferation
RET-PTC
Thyroid gland
Thyroid neoplasms
Resumé en anglais
In cancer, alteration in microRNA, small RNAs (~22nt) that regulate post-transcriptionally protein levels, exerts oncogenic role (oncomiR). OncomiRs control genes involved in cell proliferation and apoptosis, influencing cancer biology. Papillary thyroid cancer displays activating genetic alterations in MAPK signaling pathway (RET>RAS>BRAF>ERK). Using conditional induction of oncogenes in thyroid cells, we observed that RET/PTC decreases let-7 miRNA expression. In papillary thyroid cancer cell TPC-1 (with RET/PTC-1) we observed that let-7 introduction inhibits cell proliferation and ERK phosphorylation, indicating tumor suppressor role for let-7. In anaplastic thyroid cancer, we evaluate the role of introduction of miR-17-92 cluster in ARO cell line. We observed in vitro that miR-17-92 increases ARO cell proliferation and viability, acting as oncogene. However, these cells show impaired soft agar growth. In xenotransplant, ARO-miR-17-92 tumors are smaller in volume and express reduced levels of MMP-9, indicating a tumor suppressor role for the cluster.
 
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Date de Publication
2010-10-20
 
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  • FUZIWARA, Cesar Seigi, et al. Effects of let-7 microRNA on cell growth and differentiation of papillary thyroid cancer. Translational Oncology, 2009, vol. 2, n. 4, p. 236-241.
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