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1.
Oncogene ; 36(16): 2243-2254, 2017 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-27819679

RESUMO

ZNF750 controls epithelial homeostasis by regulating epidermal-differentiation genes, a role underscored by its pathogenic mutations in esophageal squamous cell cancers (SCCs). However, the precise role of ZNF750 in SCC cell biology remains unclear. In this study, we report that ZNF750 is exclusively deleted, mutated and underexpressed in human SCCs, and low ZNF750 expression is associated with poor survival. Restoration of wildtype, but not mutant ZNF750 protein uniquely inhibited the malignant phenotypes of SCC cells both in vitro and in vivo. Notably, ZNF750 promoted the expression of a long non-coding RNA (TINCR), which mediated both cancer-inhibition and differentiation-induction effects of ZNF750. In addition, ZNF750 potently suppressed cell migration by directly inhibiting the transactivation of LAMC2. Together, our findings characterize ZNF750 as a crucial SCC-specific suppressor and uncover its novel anticancer-associated functions.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Genes Supressores de Tumor , Fatores de Transcrição/genética , Animais , Carcinoma de Células Escamosas/fisiopatologia , Diferenciação Celular/genética , Linhagem Celular Tumoral , Linhagem da Célula , Movimento Celular , DNA de Neoplasias , Neoplasias Esofágicas/fisiopatologia , Feminino , Deleção de Genes , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Neoplasias de Cabeça e Pescoço/genética , Humanos , Laminina/genética , Camundongos , Camundongos Endogâmicos NOD , Mutação , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , RNA Longo não Codificante , Fatores de Transcrição/metabolismo , Transcriptoma , Proteínas Supressoras de Tumor/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/fisiopatologia
2.
Int Endod J ; 47(4): 346-55, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24033427

RESUMO

AIM: The aim of this study was to differentiate human embryonic stem cells (hESCs) into odontoblastic lineage in an optimized culture milieu. METHODOLOGY: In Phase 1, hESCs were differentiated into mesenchymal stem cells (H9-MSCs). In Phase 2, H9-MSCs were then differentiated into odontoblast-like cells (H9-Odont) under the stimulation of FGF-8 and BMP-4. Alternatively, H9-MSCs were differentiated into osteogenic lineage (H9-Osteo). In Phase 3, H9-Odont were seeded on 17% EDTA-treated dentine substrates in the presence of FGF-8 and BMP-4 for further differentiation. All experiments were performed in triplicate (n = 3). One-way anova was used to test hESC differentiation into different cell types. Post hoc Tukey's test was used to compare between groups. P < 0.05 was considered statistically significant. RESULTS: H9-Odont expressed the odontoblastic marker DSPP gene 125.47 ± 0.1 (SD)-folds higher compared with H9-MSCs at mRNA level (real-time RT-PCR). Additionally, the flow cytometry results revealed 53.1 ± 3.4 (SD) % of DSP (+) cells in H9-Odont. Alternatively, H9-Osteo expressed 5.9 ± 2.2 (SD) % of DSP (+) cells. Moreover, the SEM results demonstrated that H9-Odont were found to undergo morphological changes from a fibroblast-like shape into more rounded shapes with cytoplasmic extensions into the dentinal tubules when seeded on 17% EDTA-treated dentine substrate in the presence of FGF-8 and BMP-4. However, H9-Osteo and H9-MSCs did not show similar morphological changes under similar culture milieu. CONCLUSION: This study supports the potential of hESCs as a stable, consistent, unlimited and 'off-the-shelf' cell source to obtain odontoblastic cells for future clinical and research applications.


Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Embrionárias Humanas/citologia , Odontoblastos/citologia , Proteína Morfogenética Óssea 4/farmacologia , Diferenciação Celular/efeitos dos fármacos , Fator 8 de Crescimento de Fibroblasto/farmacologia , Citometria de Fluxo , Humanos , Técnicas In Vitro , Microscopia Eletrônica de Varredura , Fenótipo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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