RESUMEN
Acute promyelocytic leukemia (APL) is a type of acute myeloid leukemia (AML) with a high mortality rate, and the production of PML-RARα fusion protein is the cause of its pathogenesis. Our group has synthesized a novel compound, 4-amino-2-trifluoromethyl-phenyl retinate (ATPR), by structural modification of All-trans retinoic acid (ATRA), which has strong cell differentiation-inducing effects and inhibits the expression of PML-RARα. In this study, acute promyelocytic leukemia NB4 cells before and after ATPR induction were analyzed by whole transcriptome microarray, and the expression of lncRNA CONCR was found to be significantly downregulated. The role of CONCR in ATPR-induced cell differentiation and cycle arrest was explored through overexpression and silencing of CONCR. And then the database was used to predict that CONCR may bind to DEAD/H-Box Helicase 11 (DDX11) protein to further explore the role of CONCR binding to DDX11. The results showed that ATPR could reduce the expression of CONCR, and overexpression of CONCR could reverse the ATPR-induced cell differentiation and cycle blocking effect, and conversely silencing of CONCR could promote this effect. RNA immunoprecipitation (RIP) experiments showed that CONCR could bind to DDX11, the protein expression levels of DDX11 and PML-RARα were elevated after overexpression of CONCR. These results suggest that ATPR can regulate the expression of DDX11 through CONCR to affect the expression of PML-RARα fusion protein, which in turn induces the differentiation and maturation of APL cells.
Asunto(s)
Puntos de Control del Ciclo Celular , Diferenciación Celular , ARN Helicasas DEAD-box , Leucemia Promielocítica Aguda , Proteínas de Fusión Oncogénica , ARN Largo no Codificante , Transducción de Señal , Humanos , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Línea Celular Tumoral , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/genética , Tretinoina/farmacología , Regulación Leucémica de la Expresión GénicaRESUMEN
A facile confined solid-state seed-mediated alloying strategy is applied for the rational synthesis of supported Au-Ni bimetallic nanoparticles (BMNPs). The method sequentially deposits nickel salts and AuNP seeds into the ordered array of extra-large mesopores (EP-FDU-12 support) followed by a high-temperature annealing process. The size, structure, and composition of the AuNi BMNPs can be well tuned by varying the AuNP seeds, annealing temperature, and feeding ratio of metal precursors. Kinetic studies and DFT calculations suggest that the introduction of the Ni component can significantly prompt the O2 activation on AuNPs, which is critical for the selective alcohol oxidation using molecular O2 as the oxidant. The optimal Au-Ni BMNP catalyst showed the highest turnover frequency (TOF) (59â¯000 h-1, 240 °C) and highest space-time yield (STY) of benzyl aldehyde (BAD) productivity (9.23 kg·gAu-1·h-1) in the gas-phase oxidation of benzyl alcohol (BA), which is at least about 5-fold higher than that of other supported Au catalysts.
