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Sajjad Karim, Jaudah A Al-Maghrabi, Hasan M A Farsi, Ahmad J Al-Sayyad, Hans-Juergen Schulten, Abdelbaset Buhmeida, Zeenat Mirza, Alaa A Al-Boogmi, Fai T Ashgan, Manal M Shabaad, Hend F NourEldin, Khalid B M Al-Ghamdi, Adel Abuzenadah, Adeel G A Chaudhary, Mohammed H Al-Qahtani
BACKGROUND: Renal cell carcinoma (RCC) is a seventh ranked malignancy with poor prognosis. RCC is lethal at metastatic stage as it does not respond to conventional systemic treatments, and there is an urgent need to find out promising novel biomarkers for effective treatment. The goal of this study was to evaluate the biomarkers that can be potential therapeutic target and predict effective inhibitors to treat the metastatic stage of RCC. METHODS: We conducted transcriptomic profiling to identify differentially expressed genes associated with RCC...
September 30, 2016: BMC Cancer
Kran Suknuntha, Thanyatip Thita, Padma Priya Togarrati, Piyanee Ratanachamnong, Patompon Wongtrakoongate, Sirada Srihirun, Igor Slukvin, Suradej Hongeng
Wnt signaling pathway plays a major role in leukemogenesis of myeloid leukemia. Aberrancy in its regulation results in hyperactivity of the pathway contributing to leukemia propagation and maintenance. To investigate effects of Wnt pathway inhibition in leukemia, we used human leukemia cell lines (i.e., K562, HL60, THP1, and Jurkat) and several Wnt inhibitors, including XAV939, IWP2 and FH535. Our results showed that leukemia cell lines (>95 % cells) had increased endogenous levels of β-catenin as compared to mononuclear cells from healthy donors (0 %)...
October 20, 2016: International Journal of Hematology
QiuShi Wei, Jin Zhang, GuoJu Hong, ZhenQiu Chen, WeiMin Deng, Wei He, Mei Hui Chen
Icariin, the main effective component of Herba Epimedii, has been identified to regulate the osteogenic differentiation of rat bone marrow stromal cells (rBMSCs) and have potential application in preventing bone loss and promoting bone regeneration. However, the underlying signaling pathway of its osteogenic effect remains unclear. Here, we investigated whether icariin could promote osteogenesis of rBMSCs through modulating the estrogen receptor alpha (ERα) and Wnt/β-catenin signaling pathways, which implicated in rBMSCs osteogenesis...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Shasha Li, Hao Hu, Zhiheng He, Deguang Liang, Rui Sun, Ke Lan
Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is an oncogenic pathogen that displays latent and lytic life cycles. In KS lesions, infiltrated immune cells, secreted viral and/or cellular cytokines, and hypoxia orchestrate a chronic pro-lytic microenvironment that can promote KSHV reactivation. However, only a small subset of viruses spontaneously undergoes lytic replication in this pro-lytic microenvironment while the majority remains in latency. Here, we show that the expression of the Notch ligand JAG1 is induced by KSHV-encoded replication and transcription activator (RTA) during reactivation...
October 2016: PLoS Pathogens
Liming Wang, L Zhu, R Luan, L Wang, J Fu, X Wang, L Sui
Dilated cardiomyopathy (DCM) is characterized by ventricular dilatation, and it is a common cause of heart failure and cardiac transplantation. This study aimed to explore potential DCM-related genes and their underlying regulatory mechanism using methods of bioinformatics. The gene expression profiles of GSE3586 were downloaded from Gene Expression Omnibus database, including 15 normal samples and 13 DCM samples. The differentially expressed genes (DEGs) were identified between normal and DCM samples using Limma package in R language...
October 10, 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Jidong Chen, Xiaolei Cui, Zhengjiang Qian, Yanjiao Li, Kang Kang, Junle Qu, Li Li, Deming Gou
BACKGROUND: Pulmonary arterial hypertension (PAH) is a lethal disease with pronounced narrowing of pulmonary vessels due to abnormal cell proliferation. The platelet-derived growth factor BB (PDGF-BB) is well known as a potent mitogen for smooth muscle cell proliferation. To better understand how this growth factor regulates pulmonary arterial smooth muscle cells (PASMCs) proliferation, we sought to characterize the response to PDGF-BB stimulation at system-wide levels, including the transcriptome and proteome...
October 6, 2016: BMC Genomics
Xiujuan Zhang, Ying Chen, Ying Ye, Jianfeng Wang, Hong Wang, Guohong Yuan, Zhe Lin, Yihui Wu, Yan Zhang, Xinhua Lin
Wnt signaling plays essential roles in both embryonic pattern formation and postembryonic tissue homoestasis. High levels of Wnt activity repress foregut identity and facilitate hindgut fate through forming a gradient of Wnt signaling activity along the anterior-posterior axis. Here, we examined the mechanisms of Wnt signaling in hindgut development by differentiating human embryonic stem cells (hESCs) into the hindgut progenitors. We observed severe morphological changes when Wnt signaling was blocked by using Wnt antagonist Dkk1...
September 29, 2016: Cellular Signalling
Zhikui Wang, Zhaoxia Wang, Zhongqi Zhou, Yueqin Ren
BACKGROUND: This study sought to investigate crucial genes correlated with diabetic nephropathy (DN), and their potential functions, which might contribute to a better understanding of DN pathogenesis. METHODS: The microarray dataset GSE1009 was downloaded from Gene Expression Omnibus, including 3 diabetic glomeruli samples and 3 healthy glomeruli samples. The differentially expressed genes (DEGs) were identified by LIMMA package. Their potential functions were then analyzed by the GO and KEGG pathway enrichment analyses using the DAVID database...
2016: BMC Nephrology
Hongxia Qu, Liduan Zheng, Wanju Jiao, Hong Mei, Dan Li, Huajie Song, Erhu Fang, Xiaojing Wang, Shiwang Li, Kai Huang, Qiangsong Tong
Heparanase (HPSE) is the only endo-β-D-glucuronidase that is correlated with the progression of neuroblastoma (NB), the most common extracranial malignancy in childhood. However, the mechanisms underlying HPSE expression in NB still remain largely unknown. Herein, through analyzing cis-regulatory elements and mining public microarray datasets, we identified SMAD family member 4 (Smad4) as a crucial transcription regulator of HPSE in NB. We demonstrated that Smad4 repressed the HPSE expression at the transcriptional levels in NB cells...
2016: Scientific Reports
Nirpesh Adhikari, Sanjiv Neupane, Gi-Jeong Gwon, Ji-Youn Kim, Chang-Hyeon An, Sanggyu Lee, Wern-Joo Sohn, Youngkyun Lee, Jae-Young Kim
Grainyhead-like 3 (Grhl3) is a transcription factor involved in epithelial morphogenesis. In the present study, we evaluated the developmental role of Grhl3 in structural formation of the circumvallate papilla (CVP), which undergoes dynamic morphological changes during organogenesis. The specific expression pattern of Grhl3 was examined in the CVP-forming region, specifically in the apex and epithelial stalk from E13.5 to E15.5 using in situ hybridization. To determine the role of Grhl3 in epithelial morphogenesis of the CVP, we employed an in vitro tongue culture method, wherein E13...
September 1, 2016: Histochemistry and Cell Biology
Fang Yu, Roberta Rasotto, Hong Zhang, Shimin Pei, Bin Zhou, Xu Yang, Yipeng Jin, Di Zhang, Degui Lin
The Wnt signaling pathway and its key component β-catenin play critical roles in the development of diseases such as tumors in mammals. However, little is known about involvement of the Wnt/β-catenin signaling pathway in canine mammary tumors (CMTs). The present study detected the expression of 30 Wnt signaling pathway-related genes in CMTs, which are potentially useful for molecular diagnosis of CMTs and the development of new targeted therapies. Significant upregulation of DKK1, SFRP1, FZD3, β-catenin and LEF1 was detected in highly malignant CMTs compared to those in normal mammary gland tissues; while extremely significant upregulation of WNT5A was found in low malignant CMTs...
September 1, 2016: Journal of Veterinary Science
B Xu, H Zhao, C Xu
This study aimed to investigate the role and potential mechanism of miR-22 in clear cell ovarian cancer (CCOC) progression. The gene expression profile of GSE16568, including 3 CCOC samples with miR-22 overexpression and 3 negative controls, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened using the limma package in R. Gene Ontology (GO) and pathway enrichment analysis of DEGs were performed by using The Database for Annotation, Visualization and Integrated Discovery (DAVID)...
August 27, 2016: Neoplasma
Romain Désert, Sihem Mebarki, Mireille Desille, Marie Sicard, Elise Lavergne, Stéphanie Renaud, Damien Bergeat, Laurent Sulpice, Christine Perret, Bruno Turlin, Bruno Clément, Orlando Musso
Hepatocellular carcinoma (HCC) is the 3rd cause of cancer-related death worldwide. Most cases arise in a background of chronic inflammation, extracellular matrix (ECM) remodeling, severe fibrosis and stem/progenitor cell amplification. Although HCCs are soft cellular tumors, they may contain fibrous nests within the tumor mass. Thus, the aim of this study was to explore cancer cell phenotypes in fibrous nests. Combined anatomic pathology, tissue microarray and real-time PCR analyses revealed that HCCs (n=82) containing fibrous nests were poorly differentiated, expressed Wnt pathway components and target genes, as well as markers of stem/progenitor cells, such as CD44, LGR5 and SOX9...
August 18, 2016: International Journal of Biochemistry & Cell Biology
Oskar Schnappauf, Sven Beyes, Annika Dertmann, Vivien Freihen, Patrick Frey, Sabine Jägle, Katja Rose, Tom Michoel, Rudolf Grosschedl, Andreas Hecht
Transcriptional silencing is a major cause for the inactivation of tumor suppressor genes, however, the underlying mechanisms are only poorly understood. The EPHB2 gene encodes a receptor tyrosine kinase that controls epithelial cell migration and allocation in intestinal crypts. Through its ability to restrict cell spreading, EPHB2 functions as a tumor suppressor in colorectal cancer whose expression is frequently lost as tumors progress to the carcinoma stage. Previously we reported that EPHB2 expression depends on a transcriptional enhancer whose activity is diminished in EPHB2 non-expressing cells...
August 5, 2016: Biochimica et Biophysica Acta
Brian R Shy, Matthew S MacDougall, Ryan Clarke, Bradley J Merrill
CRISPR/Cas9 nucleases have enabled powerful, new genome editing capabilities; however, the preponderance of non-homologous end joining (NHEJ) mediated repair events over homology directed repair (HDR) in most cell types limits the ability to engineer precise changes in mammalian genomes. Here, we increase the efficiency of isolating precise HDR-mediated events in mouse embryonic stem (ES) cells by more than 20-fold through the use of co-incidental insertion (COIN) of independent donor DNA sequences. Analysis of on:off-target frequencies at the Lef1 gene revealed that bi-allelic insertion of a PGK-Neo cassette occurred more frequently than expected...
September 19, 2016: Nucleic Acids Research
Gui-Qing Lu, Zhi-Bo Wu, Xiao-Yan Chu, Zhi-Gang Bi, Wei-Xin Fan
BACKGROUND: Wnt and transforming growth factor-β (TGF-β) signaling pathways are known to be involved in the pathogenesis of androgenetic alopecia (AGA). However, the way that Wnt and TGF-β signaling is altered in patients with AGA and whether there exists a crosstalk between them in pathogenetic process of AGA remain unclear. OBJECTIVES: To investigate the expression of Wnt and TGF-β signaling and the crosstalk between these 2 signaling pathways in AGA. METHODS: Fifteen male patients with AGA were recruited for our research...
July 2016: Medicine (Baltimore)
Young-Eun Cho, Lawrence L Latour, Hyungsuk Kim, L Christine Turtzo, Anlys Olivera, Whitney S Livingston, Dan Wang, Christiana Martin, Chen Lai, Ann Cashion, Jessica Gill
Older age consistently relates to a lesser ability to fully recover from a traumatic brain injury (TBI); however, there is limited data to explicate the nature of age-related risks. This study was undertaken to determine the relationship of age on gene-activity following a TBI, and how this biomarker relates to changes in neuroimaging findings. A young group (between the ages of 19 and 35 years), and an old group (between the ages of 60 and 89 years) were compared on global gene-activity within 48 h following a TBI, and then at follow-up within 1-week...
2016: Frontiers in Aging Neuroscience
Dusan Hrckulak, Michal Kolar, Hynek Strnad, Vladimir Korinek
T-cell factor/lymphoid enhancer-binding factor (TCF/LEF) proteins (TCFs) from the High Mobility Group (HMG) box family act as the main downstream effectors of the Wnt signaling pathway. The mammalian TCF/LEF family comprises four nuclear factors designated TCF7, LEF1, TCF7L1, and TCF7L2 (also known as TCF1, LEF1, TCF3, and TCF4, respectively). The proteins display common structural features and are often expressed in overlapping patterns implying their redundancy. Such redundancy was indeed observed in gene targeting studies; however, individual family members also exhibit unique features that are not recapitulated by the related proteins...
July 20, 2016: Cancers
S Kuusela, H Wang, A A Wasik, H Suleiman, S Lehtonen
Inappropriate activation of the Wnt/β-catenin pathway has been indicated in podocyte dysfunction and injury, and shown to contribute to the development and progression of nephropathy. Tankyrases, multifunctional poly(ADP-ribose) polymerase (PARP) superfamily members with features of both signaling and cytoskeletal proteins, antagonize Wnt/β-catenin signaling. We found that tankyrases interact with CD2-associated protein (CD2AP), a protein essential for kidney ultrafiltration as CD2AP-knockout (CD2AP-/-) mice die of kidney failure at the age of 6-7 weeks...
2016: Cell Death & Disease
Wenxiao Han, Longmei He, Bangrong Cao, Xinhua Zhao, Kaitai Zhang, Yan Li, Paul Beck, Zhixiang Zhou, Yantao Tian, Shujun Cheng, Hongying Wang
Lef1/Tcfs family, which includes Lef1, Tcf1, Tcf3 and Tcf4, is required for the transcriptional activation induced by β-catenin. However, whether all the members play the same role in colon carcinogenesis is not clear. We found that Lef1 and Tcf1, but not Tcf3 and Tcf4, were upregulated at both mRNA and protein level with the formation of colon tumor in AOM-DSS mouse model. The same profiles were seen in human specimens with the evolvement from adenoma to adenocarcinoma. Additionally, Lef1 and Tcf1 were correlated with a subgroup of Wnt target genes, including Lgr5 a key gene of intestinal stem cell...
July 19, 2016: Molecular Carcinogenesis
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