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Summary Neurogenesis is initiated by the transient expression of the highly conserved proneural proteins, bHLH transcriptional regulators. Here, we discover a conserved post-translational switch governing the duration of proneural protein activity that is required for proper neuronal development. Phosphorylation of a single Serine at the same position in Scute and Atonal proneural proteins governs the transition from active to inactive forms by regulating DNA binding. The equivalent Neurogenin2 Threonine also regulates DNA binding and proneural activity in the developing mammalian neocortex. Using genome editing in Drosophila , we show that Atonal outlives its mRNA but is inactivated by phosphorylation. Inhibiting the phosphorylation of the conserved proneural Serine causes quantitative changes in expression dynamics and target gene expression resulting in neuronal number and fate defects. Strikingly, even a subtle change from Serine to Threonine appears to shift the duration of Atonal activity in vivo, resulting in neuronal fate defects. [ABSTRACT FROM AUTHOR]

Abstract: Wilms tumor (WT) is a genetically heterogeneous childhood kidney tumor. Several genetic mutations have been identified in WT patients, including inactivation of WTX, somatic stabilizing CTNNB1, and p53 mutations. However, the molecular mechanisms in tumorigenesis remain largely unexplored. Stat3 is a transcription factor that can promote oncogenesis. Stat3 activation is commonly viewed as crucial for multiple tumor proliferation and metastasis. We show that Stat3 is highly activated in Wilms tumor tissues compared to those in adjacent tissues. IL-6 treatment or transfection of a constitutively activated Stat3 in G401 cells promotes cell proliferation. At the molecular level, we further elucidate that Stat3 inhibits WTX expression through up-regulation of microRNA-370. Our results suggest that Stat3/miR-370/WTX regulatory axis might be a critical mechanism in Wilms tumor cells. [Copyright &y& Elsevier]

It has been certified that long noncoding RNAs (lncRNAs) are crucial regulators in the progression of various human cancers. snoRNA host gene 6 (SNHG6) has been uncovered to affect the initial stage and tumorigenesis of hepatocellular carcinoma. Nevertheless, the expression pattern and biological role of SNHG6 in glioma still need to be investigated. The study aims to investigate the expression pattern, biological role and the potential mechanism of SNHG6 in glioma. In this study, the high expression of SNHG6 was tested in both glioma tissues and glioma cells. The correlation between expression levels of SNHG6 and the overall survival of glioma patients was demonstrated by using Kaplan Meier method analysis. Next, gain of function assays revealed that overexpression of SNHG6 can promote the formation of malignant phenotype of 1800 cell. However, results of loss-of-function assays revealed that silenced SNHG6 exerted the inhibitory function on glioma cell growth. Flow cytometric analysis was performed in glioma cells to detect the anti-oncogenic effects of silenced SNHG6 on cell cycle and apoptosis. Finally, we identified that p21 was involved in glioma cell proliferation after SNHG6 was downregulated. Taken together, we concluded that SNHG6 is a regulator and a potential therapeutic target in glioma. [ABSTRACT FROM AUTHOR]