RESUMEN
Chronic lymphocytic leukemia (CLL) is a clonal proliferative disease of mature B lymphocytes. To further improve the prognosis of patients, it is necessary to further elucidate the pathogenesis of CLL and find more effective therapeutic targets. Nuclear Factor of Activated T cells 5 (NFAT5) is the major activated transcription factor (TF) upon osmotic pressure increase in mammalian cells, and it also regulates many target genes to affect various cellular functions. The effects of NFAT5 on tumor growth and metastasis have also been widely revealed. However, the effects of NFAT5 on the progression of CLL are still unclear. In this study, we found abnormally high expression of NFAT5 in human CLL patients. Additionally, NFAT5 depletion suppressed proliferation and stimulated apoptosis of CLL cells. Our data further confirmed NFAT5 regulated AQP5 expression and the phosphorylation of p38 MAPK. We also found that AQP5 overexpression reversed the inhibitory effect of NFAT5 depletion on cell proliferation in CLL cells. Furthermore, we revealed STUB1 directly bound to NFAT5 and promoted its degradation. Taken together, our results indicate the involvement of NFAT5 in CLL progression and suggest that NFAT5 could serve as a promising therapeutic target for CLL treatment.
Asunto(s)
Acuaporina 5/metabolismo , Leucemia Linfocítica Crónica de Células B/metabolismo , Factores de Transcripción/fisiología , Ubiquitina-Proteína Ligasas/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Biomarcadores de Tumor/metabolismo , Células Cultivadas , HumanosRESUMEN
Long noncoding RNAs (lncRNAs), which are prevalently transcribed in the genome, are involved in a variety of biological functions, yet little is known about their abundance in human cumulus cells (CCs) during oocyte development. Here, we describe the expression profile of lncRNAs in 3 pairs of cumulus cells from mature oocytes that result in high-quality embryo (H-CCs) and from oocytes that result in poor-quality embryo (P-CCs) using microarray analysis. In this study, a total of 20 563 lncRNAs were expressed in human CCs. One hundred and twenty four lncRNAs were consistently upregulated, and 509 lncRNAs were consistently downregulated in all samples analyzed (fold change ≥ 2.0, P < .05). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate 5 upregulated and 7 downregulated lncRNAs. The qRT-PCR results in the study were confirmed to be consistent with the microarray results. Network analysis was used for further research. The results displayed the differentially expressed lncRNAs in P-CCs between H-CCs, which suggested that lncRNAs may contribute to the processes of oocyte and early embryo development.