RESUMEN
MicroRNAs (miRNAs) have been suggested to repress transcription via binding the 3'-untranslated regions of mRNAs. However, the involvement and details of miRNA-mediated epigenetic regulation, particularly in targeting genomic DNA and mediating epigenetic regulation, remain largely uninvestigated. In the present study, transcription factor CCAAT/enhancer binding protein delta (CEBPD) was responsive to the anticancer drug bortezomib, a clinical and highly selective drug for leukemia treatment, and contributed to bortezomib-induced cell death. Interestingly, following the identification of CEBPD-induced miRNAs, we found that miR-744, miR-3154 and miR-3162 could target CpG islands in the 5'-flanking region of the CEBPD gene. We previously demonstrated that the Yin Yang 1 (YY1)/polycomb group (PcG) protein/DNA methyltransferase (DNMT) complex is important for CCAAT/enhancer binding protein delta (CEBPD) gene inactivation; we further found that Argonaute 2 (Ago2) interacts with YY1 and binds to the CEBPD promoter. The miRNA/Ago2/YY1/PcG group protein/DNMT complex linked the inactivation of CEBPD and genes adjacent to its 5'-flanking region, including protein kinase DNA-activated catalytic polypeptide (PRKDC), minichromosome maintenance-deficient 4 (MCM4) and ubiquitin-conjugating enzyme E2 variant 2 (UBE2V2), upon bortezomib treatment. Moreover, we revealed that miRNA binding is necessary for YY1/PcG group protein/DNMT complex-mediated epigenetic gene silencing and is associated with bortezomib-induced methylation on genomic DNA. The present study successfully characterized the interactions of the miRNA/Ago2/YY1/PcG group protein/DNMT complex and provided new insights for miRNA-mediated epigenetic regulation in bortezomib-induced leukemic cell arrest and cell death.
Asunto(s)
Apoptosis/efectos de los fármacos , Bortezomib/farmacología , Leucemia/fisiopatología , MicroARNs/metabolismo , Regiones no Traducidas 3' , Antineoplásicos/farmacología , Proteínas Argonautas/química , Proteínas Argonautas/metabolismo , Proteína delta de Unión al Potenciador CCAAT/genética , Proteína delta de Unión al Potenciador CCAAT/metabolismo , Línea Celular Tumoral , Islas de CpG , Metilación de ADN/efectos de los fármacos , Proteína Quinasa Activada por ADN/genética , Proteína Quinasa Activada por ADN/metabolismo , Silenciador del Gen , Humanos , Leucemia/metabolismo , Ligasas/genética , Ligasas/metabolismo , MicroARNs/genética , Componente 4 del Complejo de Mantenimiento de Minicromosoma/genética , Componente 4 del Complejo de Mantenimiento de Minicromosoma/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Regiones Promotoras Genéticas , Unión Proteica , Transcripción Genética/efectos de los fármacos , Enzimas Ubiquitina-Conjugadoras , Factor de Transcripción YY1/química , Factor de Transcripción YY1/metabolismoRESUMEN
Ferroelectric Hf x Zr1-x O2 thin films are considered promising candidates for future lead-free CMOS-compatible ferroelectric memory application. The inductive crystallization behaviors and the ferroelectric performance of Hf0.5Zr0.5O2 thin films prepared by atomic layer deposition were investigated. Inductive crystallization can be induced by the film growth condition and appropriate top electrode selection. In this work, a Ni/Hf0.5Zr0.5O2/Ru/Si stack annealed at 550°C for 30 s in N2 ambient after the Ni top electrode has been deposited was manufactured, and it shows the best ferroelectric hysteresis loop in the dielectric thickness of 25 nm, with a remanent polarization value of 6 µC/cm(2) and a coercive field strength of 2.4 MV/cm measured at 10 kHz. Endurance, retention, and domain switching current characteristics were evaluated well for potential application in the field of ferroelectric field effect transistor (FeFET) and nonvolatile ferroelectric memories (FeRAM).
RESUMEN
Graphene nanoribbons based electronic devices present many interesting physical properties. We designed and investigated the spin-dependent electron transport of a device configuration, which is easy to be fabricated, with an oxygen-terminated ZGNR central scatter region between two hydrogen-terminated ZGNR electrodes. According to the analysis based on non-equilibrium Green's function and density functional theory, the proposed device could maintain its good spin-filter performance (80% to 99%) and have a stable magneto resistance value up to 10(5)%. The spin dependent electron transmission spectrum and space-resolve density of states are employed to investigate the physical origin of the spin-polarized current and magneto resistance.