| Texto completo | |
| Autor(es): |
de Mello, Diego Claro
;
Saito, Kelly Cristina
;
Cristovao, Marcella Maringolo
;
Kimura, Edna Teruko
;
Fuziwara, Cesar Seigi
Número total de Autores: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 24, n. 9, p. 22-pg., 2023-04-26. |
| Resumo | |
Anaplastic thyroid cancer (ATC) is a rare and lethal form of thyroid cancer that requires urgent investigation of new molecular targets involved in its aggressive biology. In this context, the overactivation of Polycomb Repressive Complex 2/EZH2, which induces chromatin compaction, is frequently observed in aggressive solid tumors, making the EZH2 methyltransferase a potential target for treatment. However, the deregulation of chromatin accessibility is yet not fully investigated in thyroid cancer. In this study, EZH2 expression was modulated by CRISPR/Cas9-mediated gene editing and pharmacologically inhibited with EZH2 inhibitor EPZ6438 alone or in combination with the MAPK inhibitor U0126. The results showed that CRISPR/Cas9-induced EZH2 gene editing reduced cell growth, migration and invasion in vitro and resulted in a 90% reduction in tumor growth when EZH2-edited cells were injected into an immunocompromised mouse model. Immunohistochemistry analysis of the tumors revealed reduced tumor cell proliferation and less recruitment of cancer-associated fibroblasts in the EZH2-edited tumors compared to the control tumors. Moreover, EZH2 inhibition induced thyroid-differentiation genes' expression and mesenchymal-to-epithelial transition (MET) in ATC cells. Thus, this study shows that targeting EZH2 could be a promising neoadjuvant treatment for ATC, as it promotes antitumoral effects in vitro and in vivo and induces cell differentiation. (AU) | |
| Processo FAPESP: | 21/01674-1 - Efeito da modulação de EZH2/PRC2 no câncer de tiroide agressivo |
| Beneficiário: | Diego Claro de Mello |
| Modalidade de apoio: | Bolsas no Brasil - Mestrado |
| Processo FAPESP: | 19/25116-8 - Modulação de microRNAs e sua rede regulatória de alvos com potencial terapêutico no câncer de tiroide: aplicação da edição gênica com CRISPR/Cas9 |
| Beneficiário: | Edna Teruko Kimura |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 22/09813-3 - Análise da região promotora de EZH2 no câncer de tiroide |
| Beneficiário: | Marcella Maringolo Cristovão |
| Modalidade de apoio: | Bolsas no Brasil - Iniciação Científica |
| Processo FAPESP: | 17/01829-0 - Estudo do papel dos microRNAs na metástase através de modelos de camundongos geneticamente modificados |
| Beneficiário: | Cesar Seigi Fuziwara |
| Modalidade de apoio: | Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado |
| Processo FAPESP: | 20/10403-9 - Controle transcricional e pós-transcricional no câncer agressivo e metástase |
| Beneficiário: | Cesar Seigi Fuziwara |
| Modalidade de apoio: | Bolsas no Brasil - Jovens Pesquisadores |
| Processo FAPESP: | 19/17282-5 - Controle transcricional e pós-transcricional no câncer agressivo e metástase |
| Beneficiário: | Cesar Seigi Fuziwara |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |