The diagnostic performance of lysine(K)-specific demethylase 6B (KDM6B) in non-small cell lung cancer.

Objectives: Accumulating evidence show that histone demethylases play important roles in various types of cancers, including non-small cell lung cancer (NSCLC). In the current study, we evaluated the diagnostic value of lysine(K)-specific demethylase 6B (KDM6B) in NSCLC. Methods: Serum KDM6B expression levels of 115 NSCLC patients and 88 healthy volunteers were detected by reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between KDM6B and clinical characteristics was assessed by chi-square test. Receiver operating characteristic (ROC) analysis was applied to evaluate diagnostic efficacy. Results: Serum KDM6B was significantly lower in NSCLC patients than that in healthy controls (p < .001). Moreover, low KDM6B expression was significantly associated with the high clinical stage (p = .028) and positive lymph node metastasis (p = .031). Besides, we found that the expression of KDM6B mRNA was also significantly different among healthy controls, NSCLC early stage and later stage patients (p < .05). ROC curve indicated that KDM6B could serve as a diagnostic marker for NSCLC with the cut-off value of 0.955. The AUC was 0.897 with a sensitivity of 79.5% and specificity of 84.3%. Conclusion: Down-regulation of KDM6B is significantly associated with aggressive progression of NSCLC and KDM6B may be a tool of early detection of NSCLC.

Decreased miR-146a expression in acute ischemic stroke directly targets the Fbxl10 mRNA and is involved in modulating apoptosis.

BACKGROUND: miR-146a, a strong pro-apoptotic factor in some pathophysiological processes, is reported to be involved in ischemic stroke (IS), though its role remains unclear. Fbxl10 is an active anti-apoptotic factor and a predicted target of miR-146a. We hypothesized that dysregulation of miR-146a contributes to ischemic injury by targeting Fbxl10. METHODS: Circulating miRNAs were detected by miRNA microarray and qRT-PCR. miR-146a targets were predicted using bioinformatics and confirmed with a dual luciferase reporter assay. We used an in vitro ischemic model of oxygen-glucose deprivation and reperfusion (OGD/R) to mimic cerebral ischemia/reperfusion (I/R) conditions. Expression of miR-146a, Fbxl10 and Bcl2l2 mRNAs, and Fbxl10 and Bcl2l2 proteins was verified by qRT-PCR and Western blotting. The effects of miR-146a on neuronal cell apoptosis were evaluated by flow cytometry. RESULTS: A significant reduction in miR-146a expression was observed in acute ischemic stroke (AIS). A dual-luciferase reporter assay showed that Fbxl10, but not Bcl2l2, is a target of miR-146a. Transfection with miR-146a mimics promoted apoptosis in SK-N-SH cells and significantly reduced expression of Fbxl10. Conversely, miR-146a inhibition attenuated OGD/R-induced neuronal cell death and significantly up-regulated Fbxl10 expression. CONCLUSIONS: miR-146a expression was significantly down-regulated in AIS, and Fbxl10 was identified as a target of miR-146a. Moreover, up-regulation of Fbxl10, a miR-146a target, likely protects neurons from ischemic death.

JHDM1D and HDAC1-3 mRNA expression levels in peripheral blood mononuclear cells of patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic relapsing autoimmune disease characterized by production of autoantibodies against a series of nuclear antigens and by chronic inflammation. The etiology of SLE is the result of interactions between genetic, epigenetic, hormonal, and environmental factors. Changes in histone acetylation and methylation contribute to structural chromatin modifications. OBJECTIVE: We studied the histone demethylase JHDM1D and histone deacetylases HDAC1, HDAC2, and HDAC3 transcript levels in peripheral blood mononuclear cells (PBMCs) from patients diagnosed with systemic lupus erythematosus (SLE). Furthermore, the association of JHDM1D, HDAC1, HDAC2, and HDAC3 transcript levels with gender, age, and major clinical manifestations were analyzed. MATERIALS AND METHODS: Real-time quantitative polymerase chain reaction (RQ-PCR) analysis was used to determine JHDM1D, HDAC1, HDAC2, and HDAC3 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) from 30 patients with SLE and 36 healthy controls. RESULTS: Significantly lower HDAC2 transcript levels (p = 0.006785) and significantly higher JHDM1D (p = 0.0000002) and HDAC1 (p = 0.010581) transcript levels in SLE patients were observed compared with healthy controls. Higher JHDM1D mRNA expression was detected in active SLE patients when compared with inactive patients (p = 0.005). Furthermore, the JHDM1D transcript levels were positively correlated with disease activity (r(s) = 0.368, p = 0.045), while HDAC2 mRNA expression was positively correlated with disease duration (r(s) = 0.502, p = 0.0047). CONCLUSION: Our analyses confirmed the importance of epigenetic alterations (histone demethylation and acetylation) in SLE etiology. Moreover, our results suggest that the presence of some clinical manifestations, like hematological disease and anti-Ro antibody, might be associated with the dysregulation of histone demethylase and deacetylases mRNA expression levels.