Angiogenesis is spatially and temporally orchestrated by a myriad of signaling pathways, including the Notch signaling pathway. Here, we identified UXT as an evolutionarily conserved and developmentally expressed protein, indispensable for intersegmental vessel (ISV) formation in zebrafish. Deficiency of UXT in zebrafish embryos results in shorter ISVs, loss of tip cell behavior, and impairment of endothelial cell migration and division. Significantly, UXT attenuates the expression of the Notch-responsive genes in vitro and in vivo. Mechanistically, UXT binds to the promoters of the Notch signaling target genes and specifically interacts with the transactivation region domain of the Notch intracellular domain (NICD), impairing the interaction between NICD and the transcription factor RBP-Jκ endogenously. This prevents RBP-Jκ/CSL from activation and thus inhibits the consequent gene inductions. Furthermore, blockade of Notch signaling rescues the angiogenesis defect caused by UXT knockdown both in vitro and in vivo. Taken together, the data presented in this study characterize UXT as a novel repressor of Notch signaling, shedding new light on the molecular regulation of angiogenesis.

Objectives—To investigate the clinical characteristics, managements, outcome, and evaluate the risk factors of Multisystem (MS) Langerhans Cell Histiocytosis (LCH) with diverse skin lesions as the first sign in four young infants. Methods—Their clinical features, disease progression, therapy, and outcomes were reviewed and analyzed retrospectively. Results—The average onset age of skin lesions was about 2 months. Cases 1 and 2 had risk organs involved (RO+) and a lack of bone lesions, and progression could not be reversed by systemic chemotherapy. They both died eventually. Cases 3 and 4 (RO–) had bone involvement and were given systemic chemotherapy for a prolonged duration. Unluckily, Case 3 had a recurrence 2 years later, while Case 4’s recurrence happened nearly one year later, and diabetes insipidus one and a half years later. They both survived and are still in remission. Conclusion—MS-LCH infants with a low age of the first presentation in the skin are prone to dissemination, while RO+ is associated with high mortality. In addition, bone involvement may be a protective factor. Immunohistochemical examination of skin tissue facilitates correct early diagnosis, and adequate follow-up is necessary.

Background: Melanoma is the most lethal skin tumor. PARP1 plays an oncogenic role in tumors, but the mechanism of PARP1 in melanoma remains unclear. Explicating the functional mechanism of PARP1 might highlight new targets for improving the survival rate of melanoma patients. Methods: First, the expression level of PARP1 and its correlation with prognosis of melanoma were examined by the TCGA dataset, GEO12391 dataset, and western blot. Then, the differentially expressed genes (DEGs) after PARP1 intervention were screened by microarray slides. Also, Gene Set Enrichment Analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of DEGs were performed. At the same time, these DEGs were further compared with PARP1-related DEGs in GEO59455, and correlation analysis was performed on the intersection genes to screen PARP1 target genes. Finally, the relationship between PARP1 and its target gene was examined by western blot analysis and reverse transcription-quantitative (RT-q) PCR. CCK8 assay was used to determine the biological role of PARP1 and its target gene in melanoma. The data that support the findings of this study come from the open databases, which are acknowledged at the end of the manuscript. Results: We demonstrated that PARP1 was overexpressed in melanoma and melanoma cell lines, and upregulated expression of PARP1 was associated with higher pathological stages and unfavorable prognosis of melanoma. Five genes, including NFATc2, ITGAX, CYP26B1, SYT17, and VGF, were screened as PARP1 target genes, and NFATc2 was confirmed to be regulated by PARP1. Further CCK8 assay showed that downregulation of PARP1 or NFATc2 expression could inhibit melanoma proliferation. Conclusions: Taken together, this study demonstrated that PARP1 was a prognostic marker and contributed to melanoma proliferation through the regulation of NFATc2.