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Abstract: Daxx is a multifunctional protein, regulating a wide range of important functions including apoptosis and transcription. However, the way Daxx is regulated is poorly understood. In our previous studies, we have found that Daxx forms a complex with the E3 ubiquitin ligase Mdm2 and the de-ubiquitinase Hausp. In the present work, we show that Daxx is ubiquitinated by Mdm2 in both in vitro and in vivo systems and Mdm2 reduces Daxx expression upon over-expression. We further demonstrate that Hausp critically controls the cellular level of Daxx most likely by inducing Daxx de-ubiquitination. These results reveal Mdm2 and Hausp as important regulators for Daxx functions by controlling Daxx ubiquitination and stability. [Copyright &y& Elsevier]

Abstract: In addition to the subventricular zone, the dentate gyrus of the hippocampus is one of the few brain regions in which neurogenesis continues into adulthood. Perturbation of neurogenesis can alter hippocampal function, and previous studies have shown that neurogenesis is dysregulated in Alzheimer disease (AD) brain. Bone morphogenetic protein-4 (BMP4) and its antagonist Noggin have been shown to play important roles both in embryonic development and in the adult nervous system, and may regulate hippocampal neurogenesis. Previous data indicated that increased expression of BMP4 mRNA within the dentate gyrus might contribute to decreased hippocampal cell proliferation in the APPswe/PS1ΔE9 mouse AD model. However, it is not known whether the BMP antagonist Noggin contributes to the regulation of neurogenesis. We therefore studied the relative expression levels and localization of BMP4 and its antagonist Noggin in the dentate gyrus and whether these correlated with changes in neurogenesis in 6–12mo old APPswe/PS1ΔE9 transgenic mice. Bromodeoxyuridine (BrdU) was used to label proliferative cells. We report that decreased neurogenesis in the APP/PS1 transgenic mice was accompanied by increased expression of BMP4 and decreased expression of Noggin at both the mRNA and protein levels; statistical analysis showed that the number of proliferative cells at different ages correlated positively with Noggin expression and negatively with BMP4 expression. Intraventricular administration of a chimeric Noggin/Fc protein was used to block the action of endogenous BMP4; this resulted in a significant increase in the number of BrdU-labeled cells in dentate gyrus subgranular zone and hilus in APP/PS1 mice. These results suggest that BMP4 and Noggin co-modulate neurogenesis. [Copyright &y& Elsevier]

MicroRNAs (miRNAs) play critical roles in breast cancer cell biological processes, including proliferation and apoptosis by inhibiting the expression of their target genes. Herein, we reported that miR-630 overexpression initiates apoptosis, blocks cell cycle progression and suppresses cell proliferation in breast cancer cells. Furthermore, BMI1, a member of polycomb group family, was identified as a direct target of miR-630, and there was a negative correlation between the expression levels of BMI1 and miR-630 in human breast cancer samples. With a series of biology approaches, subsequently, we proved that BMI1 was a functional downstream target of miR-630 and mediated the property of miR-630-dependent inhibition of breast cancer progression. Taken together, these findings provide further evidence on the tumor-suppression function of miR-630 in breast cancer, and clarify BMI1 as a novel functional target gene of miR-630. [ABSTRACT FROM AUTHOR]

Abstract Background Aberrant expression of interferon regulatory factor 4 (IRF4) has been reported in several hematologic malignancies. However, the prognostic significance of IRF4 expression in esophageal squamous cell carcinoma (ESCC) remains unknown. Methods IRF4 protein expression in ESCC tumor specimens was determined immunohistochemically. The correlation of IRF4 expression with clinico-pathological features was assessed from a cohort of 100 patients with primary ESCC. Kaplan-Meier and Cox proportional regression analyses were used to evaluate the association between IRF4 expression and patient survival. Results A Kaplan-Meier analysis indicated that patients with high IRF4 expression had a significantly longer overall survival rate than those with low IRF4 expression (p = 0.0006). Furthermore, multi-variate analyses revealed that IRF4 protein expression is an independent prognostic indicator for ESCC patients. Conclusion Our results suggest that increased IRF4 protein expression correlates with improved outcome in ESCC. IRF4 may therefore represent a promising prognostic biomarker and potential immuno-therapeutic target for patients with ESCC. Highlights • Increased expression of IRF4 is closely related to improved ESCC outcome. • IRF4 serve as an independent predictor of a positive prognosis in ESCC patients. • IRF4 may represent a promising prognostic biomarker and potential immuno-therapeutic target for ESCC patients. [ABSTRACT FROM AUTHOR]