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notch gene

Yitong Xu, Hongjiu Ren, Jun Jiang, Qiongzi Wang, Muli Wudu, Qingfu Zhang, Hongbo Su, Chenglong Wang, Lihong Jiang, Xueshan Qiu
Lung cancer remains the leading cause of cancer-related death worldwide. Previous studies have shown that the novel KIAA0247 gene potentially targeted by the tumor suppressor p53 may inhibit the development of several cancers. However, the exact function of KIAA0247 in non-small-cell lung cancer (NSCLC) is unknown. The purpose of this study was to clarify the role of KIAA0247 in NSCLC. KIAA0247 expression was evaluated in tumors and adjacent normal tissues of 197 NSCLC patients by immunohistochemistry and real-time PCR and analyzed for association with clinicopathological parameters...
February 16, 2018: Cancer Science
Lars la Cour Poulsen, Reidunn Jetne Edelmann, Stig Krüger, Rodrigo Diéguez-Hurtado, Akshay Shah, Tor Espen Stav-Noraas, Anastasia Renzi, Monika Szymanska, Junbai Wang, Manuel Ehling, Rui Benedito, Monika Kasprzycka, Espen Bækkevold, Olav Sundnes, Kim S Midwood, Helge Scott, Philippe Collas, Christian W Siebel, Ralf H Adams, Guttorm Haraldsen, Eirik Sundlisæter, Johanna Hol
OBJECTIVE: Endothelial upregulation of adhesion molecules serves to recruit leukocytes to inflammatory sites and appears to be promoted by NOTCH1; however, current models based on interactions between active NOTCH1 and NF-κB components cannot explain the transcriptional selectivity exerted by NOTCH1 in this context. APPROACH AND RESULTS: Observing that Cre/Lox-induced conditional mutations of endothelial Notch modulated inflammation in murine contact hypersensitivity, we found that IL (interleukin)-1β stimulation induced rapid recruitment of RELA to genomic sites occupied by NOTCH1-RBPJ and that NOTCH1 knockdown reduced H3K27 acetylation at a subset of NF-κB-directed inflammatory enhancers...
February 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Qi Zhao, Alexandra Eichten, Asma A Parveen, Christina Adler, Ying Huang, Wei Wang, Yueming Ding, Alexander Adler, Thomas Nevins, Min Ni, Yi Wei, Gavin Thurston
Angiogenesis involves dynamic interactions between specialized endothelial tip and stalk cells that are believed to be regulated in part by VEGF and Dll4-Notch signaling. However, our understanding of this process is hampered by limited knowledge of the heterogeneity of endothelial cells and the role of different signaling pathways in specifying endothelial phenotypes. Here we characterized by single cell transcriptomics the heterogeneity of mouse endothelial cells and other stromal cells during active angiogenesis in xenograft tumors as well as from adult normal heart, following pharmacologic inhibition of VEGF and Dll4-Notch signaling...
February 15, 2018: Cancer Research
Feng Li, Jianguang Sun, Shilei Huang, Gao Su, Guofu Pi
BACKGROUND/AIMS: Osteoarthritis (OA) is the most frequently occurring joint disease and characterized by degeneration of cartilage. As the unique cell type in cartilage, chondrocytes play a crucial role during OA. Our study explored the influence of long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) on lipopolysaccharides (LPS)-induced injury in ATDC5 cells. METHODS: Cell viability, apoptosis and expression of inflammatory cytokines were all assessed to evaluate LPS-induce inflammatory injury...
February 9, 2018: Cellular Physiology and Biochemistry
Adnan I Qureshi, Muhammad T Khan, Omer Naveed, Muhammad A Saleem
Background: Several different mutations have been reported in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We present a unique case with transversion not involving cysteine on neurogenic locus notch homolog protein 3 gene. Case description: We present a case of 65-year-old woman with new ischemic stroke resulting in right hemiparesis. She has previously suffered minor strokes at age 56, 58, and 60 years and migraine headaches between age 10 and 50 years...
December 2017: Journal of Vascular and Interventional Neurology
Bo-Jeng Wang, Pei-Yi Wu, Yun-Wen Chen, Yu-Tzu Chang, Noopur Bhore, Po-Fan Wu, Yung-Feng Liao
We have developed a pair of cell-based reporter gene assays to quantitatively measure γ-secretase cleavage of distinct substrates. This manuscript describes procedures that may be used to monitor γ-secretase-mediated cleavage of either APP-C99 or Notch, using a Gal4 promoter-driven firefly luciferase reporter system. These assays were established by stably co-transfecting HEK293 cells with the Gal4-driven luciferase reporter gene and either the Gal4/VP16-tagged C-terminal fragment of APP (APP-C99; CG cells), or the Gal4/VP16-tagged Notch-ΔE (NΔE; NG cells)...
January 25, 2018: Journal of Visualized Experiments: JoVE
Daniil Nikitin, Dmitry Penzar, Andrew Garazha, Maxim Sorokin, Victor Tkachev, Nicolas Borisov, Alexander Poltorak, Vladimir Prassolov, Anton A Buzdin
Endogenous retroviruses and retrotransposons also termed retroelements (REs) are mobile genetic elements that were active until recently in human genome evolution. REs regulate gene expression by actively reshaping chromatin structure or by directly providing transcription factor binding sites (TFBSs). We aimed to identify molecular processes most deeply impacted by the REs in human cells at the level of TFBS regulation. By using ENCODE data, we identified ~2 million TFBS overlapping with putatively regulation-competent human REs located in 5-kb gene promoter neighborhood (~17% of all TFBS in promoter neighborhoods; ~9% of all RE-linked TFBS)...
2018: Frontiers in Immunology
Chad J Creighton, Fengju Chen, Yiqun Zhang, Don L Gibbons, Benjamin Deneen, David Kwiatkowski, Michael Ittmann
PURPOSE: The Cancer Genome Atlas data resources represent an opportunity to explore commonalities across cancer types involving multiple molecular levels, but tumor lineage and histology can represent a barrier in moving beyond differences related to cancer type. EXPERIMENTAL DESIGN: On the basis of gene expression data, we classified 10224 cancers, representing 32 major types, into ten molecular-based "classes."  Molecular patterns representing tissue or histologic dominant effects were first removed computationally, with the resulting classes representing emergent themes across tumor lineages...
February 9, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
James R Gilbert, Gwen M Taylor, Joseph E Losee, Mark P Mooney, Gregory M Cooper
OBJECTIVE: Craniosynostosis (CS) involves the premature fusion of one or more cranial sutures. The etiology of CS is complex and mutations in more than 50 distinct genes have been causally linked to the disorder. Many of the genes that have been associated with CS in humans play an essential role in tissue patterning and early craniofacial development. Among these genes are members of the Hedgehog (HH) and Notch signal transduction pathways, including the GLI family member Gli3, Indian Hedgehog ( Ihh), the RAS oncogene family member Rab23, and the Notch ligand JAGGED1 ( Jag1)...
March 2018: Cleft Palate-craniofacial Journal
Q Zeng, Y Wan, P Zhu, M Zhao, F Jiang, J Chen, M Tang, X Zhu, Y Li, H Zha, Y Wang, M Hu, X Mo, Y Zhang, Y Deng, Y Chen, X Fan, Y Chen, X Ye, R Bodmer, K Ocorr, Z Jiang, J Zhuang, W Yuan, X Wu
The basic helix-loop-helix (bHLH) protein families are a large class of transcription factors, which are associated with cell proliferation, tissue differentiation, and other important development process. We reported that the Nuclear localized protein-1 (Nulp1) might act as a novel bHLH transcriptional factor to mediate cellular functions. However, its role in development in vivo remains unknown. Here we show that Drosophila Nulp1 (dNulp1) mutants, generated by CRISPR/Cas9 targeting the Domain of Unknown Function (DUF654) in its C terminal, are partially homozygous lethal and the rare escapers have bent femurs, which are similar to the major manifestation of congenital bent-bone dysplasia in human Stuve-Weidemann syndrome...
February 12, 2018: Current Molecular Medicine
Shubing Zhang, Jingjiang Liu, Keli Xu, Zhijian Li
Pancreatic cancer is one of the leading causes of cancer-associated mortality. The understanding of the expression pattern of key protein factors and their function in pancreatic cancer cells is therefore vital for the diagnosis and treatment of this malignancy. The results of the present study reveal that the levels of neurogenic locus notch homolog protein 2 (Notch2) and phosphorylated (p)-SMAD family member 2 decreased, whereas the expression of Notch3 and phosphoinositide-3 kinase catalytic subunit-γ protein increased in human pancreatic cancer tissues compared with tumor-adjacent tissues...
February 2018: Oncology Letters
Ann-Kathrin Ernst, Annika Putscher, Timur R Samatov, Anna Suling, Vladimir V Galatenko, Maxim Yu Shkurnikov, Evgeny N Knyazev, Alexander G Tonevitsky, Thomas Haalck, Tobias Lange, Hanna Maar, Jennifer Schröder-Schwarz, Kristoffer Riecken, Udo Schumacher, Daniel Wicklein
Finding additional functional targets for combination therapy could improve the outcome for melanoma patients. In a spontaneous metastasis xenograft model of human melanoma a shRNA mediated knockdown of L1CAM more than sevenfold reduced the number of lung metastases after the induction of subcutaneous tumors for two human melanoma cell lines (MeWo, MV3). Whole genome expression arrays of the initially L1CAM high MeWo subcutaneous tumors revealed unchanged or downregulated genes involved in epithelial to mesenchymal transition (EMT) except an upregulation of Jagged 1, indicating a compensatory change in Notch signaling especially as Jagged 1 expression showed an increase in MeWo L1CAM metastases and Jagged 1 was expressed in metastases of the initially L1CAM low MV3 cells as well...
2018: PloS One
Lina Xu, Lina Gu, Xufeng Tao, Youwei Xu, Yan Qi, Lianhong Yin, Xu Han, Jinyong Peng
BACKGROUND: Development of novel candidates to promote liver regeneration is critical important after partial hepatectomy (PH). Dioscin, a natural product, shows potent effect on liver protection in our previous works. PURPOSE: This work aimed to investigate the effect and underlying mechanisms of dioscin on liver regeneration. METHODS: The promoting proliferation effects of dioscin on mouse hepatocytem AML12 cells, rat primary hepatocytes, rats and mice after 70% PH were evaluated...
January 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Byung-Kwon Jung, Chul-Woo Park, Kwon-Yul Ryu
Reduced levels of cellular ubiquitin (Ub) pools due to disruption of the polyubiquitin gene Ubb lead to dysregulation of neural stem cell (NSC) differentiation and impaired neuronal maturation in cells isolated from Ubb -/- mouse embryonic brains. However, it is currently unknown whether Ub is required for the specific stage of neuronal development or whether it plays a pleiotropic role throughout the process. To answer this question, we aimed to downregulate Ubb expression temporally during neuronal development, which could not be achieved in Ubb -/- cells...
February 8, 2018: Scientific Reports
Lianjie Miao, Jingjing Li, Jun Li, Xueying Tian, Yangyang Lu, Saiyang Hu, David Shieh, Ryan Kanai, Bo-Yang Zhou, Bin Zhou, Jiandong Liu, Anthony B Firulli, James F Martin, Harold Singer, Bin Zhou, Hongbo Xin, Mingfu Wu
Hey2 gene mutations in both humans and mice have been associated with multiple cardiac defects. However, the currently reported localization of Hey2 in the ventricular compact zone cannot explain the wide variety of cardiac defects. Furthermore, it was reported that, in contrast to other organs, Notch doesn't regulate Hey2 in the heart. To determine the expression pattern and the regulation of Hey2, we used novel methods including RNAscope and a Hey2 CreERT2 knockin line to precisely determine the spatiotemporal expression pattern and level of Hey2 during cardiac development...
February 8, 2018: Scientific Reports
Juan-Li Duan, Bai Ruan, Xian-Chun Yan, Liang Liang, Ping Song, Zi-Yan Yang, Yuan Liu, Ke-Feng Dou, Hua Han, Lin Wang
Liver sinusoidal endothelial cells (LSECs) critically regulate liver homeostasis and diseases through angiocrine factors. Notch is critical in endothelial cells (ECs). In the current study, Notch signaling was activated by inducible EC-specific expression of the Notch intracellular domain (NIC). We found that endothelial Notch activation damaged liver homeostasis. Notch activation resulted in decreased fenestration and increased basement membrane, and a gene expression profile with decreased LSEC-associated genes and increased continuous EC-associated genes, suggesting LSEC dedifferentiation...
February 8, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Muhammad Ikram, Yeseon Lim, Sun-Yong Baek, Songwan Jin, Young Hun Jeong, Jong-Young Kwak, Sik Yoon
Lymphoma is a heterogeneous disease with a highly variable clinical course and prognosis. Improving the prognosis for patients with relapsed and treatment-resistant lymphoma remains challenging. Current in vitro drug testing models based on 2D cell culture lack natural tissue-like structural organization and result in disappointing clinical outcomes. The development of efficient drug testing models using 3D cell culture that more accurately reflects in vivo behaviors is vital. Our aim was to establish an in vitro 3D lymphoma model that can imitate the in vivo 3D lymphoma microenvironment...
January 5, 2018: Oncotarget
Li Pan, Hongli Yang, Wenqiang Tang, Cong Xu, Shuangfeng Chen, Zhen Meng, Keyi Li, Haiying Chen
Zinc-finger protein 750 (ZNF750) is the potential anti-cancer gene in oral squamous cell carcinoma (OSCC). The present study was to investigate the expression changes of ZNF750 in OSCC tissue and to reveal the induction of altered mRNA expression profiles caused by over-expressed ZNF750 in CAL-27 cell. The expression level of ZNF750 in tissue specimens from OSCC patients was detected by immunohistochemistry. Gene expression profiling was performed using Human Signal Transduction PathwayFinder RT 2 Profiler™ PCR Array...
January 2, 2018: Oncotarget
Diana Kim, Vivian Lee, Taylor Dorsey, Laura Niklason, Liqiong Gui, Guohao Dai
Pluripotent stem cell derived endothelial cells (ECs) have great potential to be used in vascular therapy or tissue engineering. It is also much desired to obtain arterial or venous ECs for specific applications. Factors that are critical for the proper arterial or venous differentiation from pluripotent stem cells are still need to be understood. Here, we aim to investigate this problem deeper by examining neuropilin-1 (Nrp1), an early arterial marker that may be critical for arterial cell fate commitment...
February 7, 2018: Stem Cells and Development
Nunthawan Nowwarote, Phunphimp Chanjavanakul, Pattanit Kongdecha, Panipuk Clayhan, Sujin Chumprasert, Jeeranan Manokawinchoke, Hiroshi Egusa, Prasit Pavasant, Thanaphum Osathanon
OBJECTIVE: The aim of the present study was to develop a Jagged1-coated polycaprolactone (PCL) membrane and to evaluate the response of human periodontal ligament cells (hPDL) on this membrane in vitro. METHODS: Membranes were prepared from PCL and PCL-incorporated hydroxyapatite (PCL/HA). The membranes' surface roughness, surface wettability, and mechanical properties were examined. An indirect affinity immobilization technique was used to coat the membranes with Jagged1...
January 21, 2018: Archives of Oral Biology
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