Endometrial cancer features abnormal growth of cells of the inner lining of the uterus with the potential to invade to other organs. Accumulating evidence suggests that aberrant expression of long non-coding RNA (lncRNA) may facilitate cancer progression. The aim of the present study was to identify the molecular mechanisms of the lncRNA known as DLX6 antisense RNA 1 (DLX6-AS1) in endometrial cancer. Microarray-based analysis was utilized to predict expression profile and possible function pattern of DLX6-AS1 and DLX6 in endometrial cancer, and their expression was quantified in 78 clinically obtained endometrial cancer tissues and also in cell lines. We next assessed the effects of DLX6-AS1 and DLX6 on proliferation, invasion and apoptosis of endometrial cancer cells. A mouse xenograft model was established to confirm DLX6-AS1 functions and explore its underlying regulatory mechanisms in vivo. DLX6-AS1 and DLX6 were highly expressed in endometrial cancer tissues and cells, and their silencing weakened the proliferative and invasive abilities of endometrial cancer cells and tumours, while promoting apoptosis. Mechanistic investigations indicated that DLX6-AS1 formed a triplex structure with DLX6 via interaction with p300/E2F1 acetyltransferase. Thus, we find that functional up-regulation of DLX6-AS1 can promote endometrial cancer progression via a novel triplex mechanism that may prove to be great clinical significance for future treatments of endometrial cancer.

Cyclin-dependent kinase-5 (CDK5) is activated by p35 and then binds to both p35 and its truncated form p25 to promote hyperphosphorylation of tau protein, thereby facilitating the pathological progression of Alzheimer\'s disease (AD). However, it is unknown whether a patient\'s diabetic status promotes the later onset of AD in a CDK5-dependent manner. Here, we induced pro-diabetic insulin resistance and glucose intolerance in rats using a combined high fat and high glucose diet. Compared to normal diet-fed rats, these pro-diabetic rats exhibited poorer behavioral performance in the Morris water maze test and the novel object recognition test. Increased phosphorylation of tau protein was detected in the hippocampal CA1 region of the rat brain, suggesting neurodegeneration. Moreover, CDK5 transcriptional activity was significantly increased in the HFGD-rat brain, likely resulting from an increase in acetylation and a decrease in methylation of the CDK5 promoter. Together, these data suggest that epigenetic control of the CDK5 promoter by acetylation and methylation may regulate the diabetes-associated development of AD.

Histone deacetylase (HDAC) inhibitors have been associated primarily with an anti-proliferative effect in vitro and in vivo. Recent data provide evidence for an anti-inflammatory potency of HDAC inhibitors in models of experimental colitis. Because the balance of T cell subpopulations is critical for the balance of the mucosal immune system, this study explores the regulatory potency of HDAC inhibitors on T cell polarization as a mechanistic explanation for the observed anti-inflammatory effects. Although HDAC inhibition suppressed the polarization toward the pro-inflammatory T helper 17 (Th17) cells, it enhanced forkhead box P3 (FoxP3)(+) regulatory T cell polarization in vitro and in vivo at the site of inflammation in the lamina propria. This was paralleled by a down-regulation of the interleukin 6 receptor (IL-6R) on naïve CD4(+) T cells on the mRNA as well as on the protein level and changes in the chromatin acetylation at the IL6R gene and its promoter. Downstream of the IL-6R, HDAC inhibition was followed by a decrease in STAT3 phosphorylation as well as retinoic acid receptor-related orphan receptor γT (RORγT) expression, thus identifying the IL-6/STAT3/IL-17 pathway as an important target of HDAC inhibitors. These results directly translated to experimental colitis, where IL-6R expression was suppressed in naïve T cells, paralleled by a significant reduction of Th17 cells in the lamina propria of ITF2357-treated animals, resulting in the amelioration of disease. This study indicates that, in experimental colitis, inhibition of HDAC exerts an anti-inflammatory potency by directing T helper cell polarization via targeting the IL-6 pathway.