Human DACT3 blocking peptide

Dact3 is a negative regulator of Wnt/beta-catenin signaling. c-Myb promotes tumor cell invasion through Wnt/beta-catenin pathway. However, the detailed mechanism by which Dact3 and c-Myb modulate the progression of non-small cell lung cancer (NSCLC) remains unclear. In this study, the expressions of Dact3 and c-Myb in 254 surgically resected NSCLC samples were detected by immunohistochemistry. We transfected Dact3 cDNA to A549 and H157 cells or siRNA-Dact3 to SPC cells and examined above effects on the activity of Wnt/beta-catenin signaling by Western blot and luciferase activity assay, in addition to cell biological behavior by Transwell and MTT assay. Dact3 expression was reduced in NSCLC tissue. Reduced Dact3 expression was correlated with lymph node metastasis and poor prognosis of NSCLC (P<0.05). In addition, Dact3 expression was negatively correlated with the c-Myb expression (R = -0.626, P<0.05). Dact3 transfection resulted in c-Myb reduced expression in NSCLC cells, as well as decreased activity of Wnt/beta-catenin signaling and reduced cell invasive and proliferative capacity. siRNA-Dact3 transfection had the opposite effect. Our results indicate that Dact3 may inhibit the malignant phenotype of NSCLC through downregulation of c-Myb.

Phthalates are endocrine-disrupting chemicals that can cross the placenta and affect the fetal epigenome. Among various epigenetic regulators of gene expression, long noncoding RNAs (lncRNAs) are important players that may also be involved in the manifestation of endocrine-disrupting chemical toxicity. We sought to explore the association between maternal urinary phthalate metabolite concentrations and lncRNA expression in human placenta to better understand potential mechanisms through which lncRNAs participate in mediating phthalate toxicity. Ten patients with uncomplicated dichorionic diamniotic twin pregnancies at term were included in this study. Urinary (n = 10) and placenta samples (n = 20) were collected for all participants. Urinary samples were analyzed for 15 phthalate metabolites and 2 phthalate alternative metabolites. Real-time PCR arrays were used to identify and quantify 87 lncRNAs from the placental samples. We tested the Spearman correlation matrix to compare prenatal phthalate measures against placental lncRNA levels. lncRNA levels showed large variations across samples, with no significant differences in lncRNA expression within twin pairs. Mono-(carboxynonyl) phthalate demonstrated consistently strong correlations with most lncRNAs. The strongest correlation was observed between mono-hydroxyisobutyl phthalate and LOC91450 (R-spearman = 0.88, p < .001). This correlation remained significant after Bonferroni adjustment. Other strong correlations were observed between mono-isobutyl phthalate, DPP10 and HOTTIP (R-spearman = -0.91, p < .001). AIRN, DACT3.AS1, DLX6, DPP10, HOTTIP, LOC143666, and LOC91450 were strongly correlated with the greatest number of phthalate metabolites. Further studies are needed to validate these results and understand if the altered expression of lncRNAs in human placenta has clinical significance.