Lack of cellular differentiation is a key feature of nasopharyngeal carcinoma (NPC), but it also presents as a unique opportunity for intervention by differentiation therapy. Here using RNA-seq profiling analysis and functional assays, we demonstrate that reduced IKKa expression is responsible for the undifferentiated phenotype of NPC. Conversely, overexpression of IKKa induces differentiation and reduces tumorigenicity of NPC cells without activating NF-kB signalling. Importantly, we describe a mechanism whereby EZH2 directs IKKa transcriptional repression via H3K27 histone methylation on the IKKa promoter. The differentiation agent, retinoic acid, increases IKKa expression by suppressing EZH2-mediated H3K27 histone methylation, resulting in enhanced differentiation of NPC cells. In agreement, an inverse correlation between IKKa (low) and EZH2 (high) expression is associated with a lack of differentiation in NPC patient samples. Collectively, these findings demonstrate a role for IKKa in NPC differentiation and reveal an epigenetic mechanism for IKKa regulation, unveiling a new avenue for differentiation therapy.
Nasopharyngeal carcinoma (NPC) is one of the severe head and neck carcinomas, which is rare in west countries but has high incidence in Southern Asia especially South China. Although NPC is relatively sensitive to radiotherapy, the prognosis of patients is poor due to the advanced stage at the time of diagnosis. Therefore, it is important to understand the mechanisms involved in tumorigenesis and develop early diagnostic techniques. S-phase kinase associated protein 2 (Skp2) is overexpressed in several human cancers and associates with poor prognosis. However, its function in NPC has not been fully addressed. In this study we found Skp2 was highly expressed in NPC specimen and correlated with poor prognosis. We generated Skp2 knockdown cells to further delineate its role in NPC development. Knockdown of Skp2 partially reduced cell proliferation, promoted cellular senescence, and decreased the population of stem cell like aldehyde dehydrogenase1 positive cells as well as their self-renewal ability. Our study not only interprets the predictive role of Skp2 in the poor prognosis of NPC patients, but also reveals that Skp2 regulates the NPC cancer stem cell maintenance, which shed lights on the target therapy and early diagnosis of NPC in clinical application.
In order to improve the cleaning efficiency of curtain wall, a pneumatic robot is designed. The robot is consists of mobile system, adsorption system and cleaning system. The mobile system is a cross-shaped framework that is driven by the pneumatic system and moves mutually. Vacuum sucker scheme is adopted in the adsorption system. Cleaning brush is driven directly backward and forward by the cylinder. The adsorption and detachment of robot feet sucker, body movement and sequence control of the robot cleaning task are controlled by the PLC. The function that robot can clean glass curtain wall efficiently by the harmony operation is achieved.
Various ceramics were prepared by the conventional solid-state reaction technique according to the compositional formula of (1-x) BaTiO3+xCuO withx= 0.00 ~ 0.05. The influence of CuO additive on microstructure, crystalline structure and dielectric and piezoelectric properties were investigated. It has been found that CuO acts like a sintering aid in the CuO-modified BaTiO3ceramics to promote the ceramic densification and suppress the abnormal grain growth during sintering process, and decreases the orthorhombic-tetragonal phase transition temperature. The CuO-modified BaTiO3ceramics show desirable microstructures with high density, small average grain size and uniform grain size distribution. For the one withx= 0.01, it has the good piezoelectric properties ofd33= 300 pC/N,kp= 0.49,k33= 0.62 andQm= 425 at room temperature, and exhibits aε'peak at -5°C and ad33maximum of 353 pC/N at 0°C, respectively.
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