Role of long noncoding RNA AC073046.25 in regulation of systemic lupus erythematosus susceptibility gene TET3 expression / 上海交通大学学报（医学版）

Objective: To investigate the regulatory effect of long noncoding RNA (lncRNA) AC073046.25 on the expression of Tet methylcytosine dioxygenase 3 (TET3) in monocytes, and analyze the feasibility of AC073046.25 as a biomarker for the diagnosis of systemic lupus erythematosus (SLE). Methods: The cell specificity and function of AC073046.25 were predicted by epigenetic modification and cytoplasm/nuclear location experiment. In U-937 cells, antisense oligonucleotide (ASO) was used to knock down AC073046.25. The effect of ASO knockdown on TET3 expression was analyzed by quantitative real-time PCR. Monocytes from healthy volunteers (n=32) and SLE patients (n=46) were collected. The correlation between AC073046.25 and TET3 expression was analyzed by Pearson coefficient. Healthy volunteers were included in the healthy control group, and the SLE patients were divided into SLE-inactive group and SLE-active group according to the systemic lupus erythematosus disease activity index (SLEDAI). The differences of AC073046.25 and TET3 expression in healthy control group and different disease activity groups were compared by unpaired bilateral student's t test. Results: The epigenetic modification and cytoplasm/nuclear location experiment showed that AC073046.25 may be involved in the regulation of TET3 expression in monocytes. In U-937 cells, after ASO knocked down AC073046.25, TET3 expression level decreased (both P=0.002 in ASO groups). Correlation analysis showed that AC073046.25 expression was positively correlated with TET3 expression in primary monocytes (r=0.650, P=0.000). Unpaired bilateral student's t test showed that the expression level of AC073046.25 in the SLE-active group was lower than that in the healthy control group (P=0.002) and the SLE-inactive group (P=0.000). Conclusion: In monocytes, AC073046.25 can regulate the expression of TET3, and its expression is significantly decreased in monocytes derived from disease active SLE patients, which implicating that AC073046.25 can be thought as a biomarker for SLE disease activity diagnosis.

Research progress of epigenetic regulation of vascular diseases / 中国胸心血管外科临床杂志

@#Epigenetics refers to heritable changes in gene expression independent of DNA nucleotide sequence itself, and the main mechanisms include DNA methylation, histone modifications, noncoding RNAs, and so on. Vascular disease is a chronic disease regulated by the interaction between environmental and genetic factors. In recent years, more and more studies have confirmed that epigenetic regulation plays an important role in the occurrence and development of vascular diseases. This article reviews recent advances in epigenetics in vascular disease.

TET2 is upregulated during erythroid differentiation of CD34+ cells from healthy donors and myelodysplastic syndrome patients

Background: Tet methylcytosine dioxygenase 2 (TET2) is frequently mutated and/or downregulated in myeloid neoplasm, including myelodysplastic syndromes. Despite the extensive studies, the specific contribution of TET2 in disease phenotype of myeloid neoplasms is not fully elucidated. Recent findings have grown attention on the role of TET2 in normal and malignant erythropoiesis. Methods: In the present study, we investigated TET2 mRNA levels by quantitative PCR during erythropoietin-induced erythroid differentiation CD34+ cells from healthy donor and myelodysplastic syndrome patients. Statistical analyses were performed using the ANOVA and Bonferroni post hoc test and a p-value <0.05 was considered statically significant. Results: TET2 expression is upregulated during erythroid differentiation of CD34+ cells from healthy donor and myelodysplastic syndrome patients. Conclusions: Our findings corroborate that TET2 is involved in the erythrocyte differentiation (AU)

Non-catalytic roles for TET1 protein negatively regulating neuronal differentiation through srGAP3 in neuroblastoma cells

The methylcytosine dioxygenases TET proteins (TET1, TET2, and TET3) play important regulatory roles in neural function. In this study, we investigated the role of TET proteins in neuronal differentiation using Neuro2a cells as a model. We observed that knockdown of TET1, TET2 or TET3 promoted neuronal differentiation of Neuro2a cells, and their overexpression inhibited VPA (valproic acid)-induced neuronal differentiation, suggesting all three TET proteins negatively regulate neuronal differentiation of Neuro2a cells. Interestingly, the inducing activity of TET protein is independent of its enzymatic activity. Our previous studies have demonstrated that srGAP3 can negatively regulate neuronal differentiation of Neuro2a cells. Furthermore, we revealed that TET1 could positively regulate srGAP3 expression independent of its catalytic activity, and srGAP3 is required for TET-mediated neuronal differentiation of Neuro2a cells. The results presented here may facilitate better understanding of the role of TET proteins in neuronal differentiation, and provide a possible therapy target for neuroblastoma.