BackgroundThe histone H3K27 demethylases UTX and JMJD3 are important regulatory factors that modulate gene expression by altering the physical state of chromatin. Previous studies have indicated an abnormal H3K27 methylation status in carcinogenesis. We therefore investigated the expression patterns of UTX and JMJD3 in renal cell carcinoma (RCC) and their roles in cancer development.MethodsThe mRNA expression levels of the UTX and JMJD3 genes were determined in cancer tissues and adjacent normal tissues in 36 patients with primary RCC, using quantitative real-time-polymerase chain reaction. The UTX and JMJD3 protein contents were measured by western blotting and immunohistochemical analysis.ResultsUTX and JMJD3 transcripts were significantly increased in cancer tissues compared to normal tissues (P < 0.05). mRNA levels of the inhibitor of cyclin-dependent kinases 4 and 6 p16INK4a were also increased in cancer tissues (P < 0.001). Western blotting indicated that levels of both demethylases were increased in cancer tissues. The level of tri-methylated H3K27 (H3K27me3) was lower in cancer tissues compared to normal tissues, but expression of the H3K27 methyltransferase EZH2 was increased (P < 0.05). These results suggest that the two H3K27 demethylases may play critical roles in the regulation of H3K27 methylation status in RCC. Immunohistochemical analysis confirmed that UTX and JMJD3 expression were upregulated in cancer tissues compared to adjacent tissues.ConclusionsThis study demonstrated that UTX and JMJD3 were upregulated in cancer tissues, suggesting that they may be involved in the development of primary RCC. The potential roles of H3K27 demethylases as biomarkers in the early diagnosis of RCC need to be further explored.

Alcoholic liver disease (ALD) is a serious liver problem in western countries. Our previous study has demonstrated that vitamin C plays a protective role in ALD. The vitamin C homeostasis is tightly regulated by sodium-dependent vitamin C transporters (SVCTs) 1 and 2. But the role of two SVCTs in ALD is less understood. In this study, we examined the expression patterns of two SVCTs in mice after alcohol consumption. Our results suggested that alcohol consumption obviously increased the expression of two SVCTs in liver and SVCT1 in kidney and intestine, which is important for vitamin C absorption. Vitamin C supplement increased the sera vitamin C content and ameliorated the symptom of ALD. Intestinal absorption and renal re-absorption mediated by SVCT1 are key factors to increase the sera vitamin C content after alcohol consumption. We proposed that both reactive oxygen species and low vitamin C concentration regulate the expression of SVCTs, and the protective role of vitamin C is mediated by suppressing the stability of hypoxia-inducible factor-1a. Thus, our study is significant for the understanding of vitamin C homeostasis in ALD and for better use of other antioxidants in ALD therapy.

Abnormal expression of histone demethylase Jumonji domain-containing protein 1A (JMJD1A) is associated with many kinds of cancers. JMJD1A is also a hypoxic response gene and its expression is regulated by hypoxia-inducible factor-1a . In this study, we determined the role of JMJD1A in development and hypoxia pathway. We also measured the expression of JMJD1A and two hypoxia factors glucose transporter 1 (GLUT1) and vascular endothelial growth factor (VEGF) in 786-0 and HEK293 cells treated with different concentrations of NiCl 2 (2.5 -100 mM) for 24 h, and found that JMJD1A mRNA and protein were up-regulated with increased concentrations of NiCl 2 . We then observed that ascorbate could retard the up-regulated effect of NiCl 2 -induced JMJD1A expression in a dose-dependent manner through decreasing the stability of HIF-1a protein.Immunohistochemical analysis further demonstrated ascorbate antagonized Ni 21 -induced up-regulation of JMJD1A expression in 786-0, HEK293, and OS-RC-2 cells. These findings suggest that both Ni 21 and ascorbate can regulate the expression of histone demethylase JMJD1A, which is important for cancer development or inhibition.