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https://www.readbyqxmd.com/read/27908728/activation-of-evi1-transcription-by-the-lef1-%C3%AE-catenin-complex-with-p53-alteration-in-myeloid-blast-crisis-of-chronic-myeloid-leukemia
#1
Nawin Manachai, Yusuke Saito, Shingo Nakahata, Avinash Govind Bahirvani, Tomomi Osato, Kazuhiro Morishita
The presence of a BCR-ABL1 fusion gene is necessary for the pathogenesis of chronic myeloid leukemia (CML) through t(9;22)(q34;q11) translocation. Imatinib, an ABL tyrosine kinase inhibitor, is dramatically effective in CML patients; however, 30% of CML patients will need further treatment due to progression of CML to blastic crisis (BC). Aberrant high expression of ecotropic viral integration site 1 (EVI1) is frequently observed in CML during myeloid-BC as a potent driver with a CML stem cell signature; however, the precise molecular mechanism of EVI1 transcriptional regulation during CML progression is poorly defined...
November 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27906112/chromatin-wide-and-transcriptome-profiling-integration-uncovers-p38%C3%AE-mapk-as-a-global-regulator-of-skeletal-muscle-differentiation
#2
Jessica Segalés, Abul B M M K Islam, Roshan Kumar, Qi-Cai Liu, Pedro Sousa-Victor, F Jeffrey Dilworth, Esteban Ballestar, Eusebio Perdiguero, Pura Muñoz-Cánoves
BACKGROUND: Extracellular stimuli induce gene expression responses through intracellular signaling mediators. The p38 signaling pathway is a paradigm of the mitogen-activated protein kinase (MAPK) family that, although originally identified as stress-response mediator, contributes to establishing stem cell differentiation fates. p38α is central for induction of the differentiation fate of the skeletal muscle stem cells (satellite cells) through not fully characterized mechanisms. METHODS: To investigate the global gene transcription program regulated by p38α during satellite cell differentiation (myogenesis), and to specifically address whether this regulation occurs through direct action of p38α on gene promoters, we performed a combination of microarray gene expression and genome-wide binding analyses...
March 15, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27903773/nlk-mediated-phosphorylation-of-hdac1-negatively-regulates-wnt-signaling
#3
Katarzyna Chmielarska Masoumi, Renée Daams, Wondossen Sime, Valentina Siino, Hengning Ke, Fredrik Levander, Ramin Massoumi
The Wnt signaling pathway is essential in regulating various cellular processes. Different mechanisms of inhibition for Wnt signaling have been proposed. Besides β-catenin degradation, through the proteasome, nemo-like kinase (NLK) is another molecule that is known to negatively regulate Wnt signaling. However, the mechanism by which NLK mediates the inhibition of Wnt signaling is not yet known. In the present study, we used primary embryonic fibroblast cells isolated from NLK-deficient mice and showed that these cells proliferate faster and have a shorter cell cycle compared with wild-type cells...
November 30, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27903708/astrocyte-elevated-gene-1-regulates-beta-catenin-signaling-to-maintain-glioma-stem-like-stemness-and-self-renewal
#4
Bin Hu, Luni Emdad, Timothy P Kegelman, Xue-Ning Shen, Swadesh K Das, Devanand Sarkar, Paul B Fisher
: Glioblastoma multiforme (GBM) is a common malignant brain tumor that portends extremely poor patient survival. Recent studies reveal that glioma stem-like cells (GSCs) are responsible for GBM escape from chemo-radiotherapy and mediators of tumor relapse. Previous studies suggest that AEG-1 (MTDH), an oncogene upregulated in most types of cancers including GBM, plays a focal role linking multiple signaling pathways in tumorigenesis. We now report a crucial role of AEG-1 in glioma stem cell biology...
November 30, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27901484/gene-expression-profiling-of-hematologic-malignant-cell-lines-resistant-to-oncolytic-virus-treatment
#5
Nam Hee Lee, Mikyung Kim, Sung Yong Oh, Seong-Geun Kim, Hyuk-Chan Kwon, Tae-Ho Hwang
Pexa-Vec (pexastimogene devacirpvec; JX-594) has emerged as an attractive tool in oncolytic virotherapy. Pexa-Vec demonstrates oncolytic and immunotherapeutic mechanisms of action. But the determinants of resistance to Pexa-Vec are mostly unknown. We treated hemoatologic malignant cells with Pexa-Vec and examined the gene-expression pattern of sensitive and resistant cells. Human myeloid malignant cell lines (RPMI-8226, IM-9, K562, THP-1) and lymphoid cancer cell lines (MOLT4, CCRF-CEM, Ramos, U937) were treated with Pexa-Vec...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27834469/the-expression-of-fat1-is-associated-with-overall-survival-in-children-with-medulloblastoma
#6
Jianzhong Yu, Hao Li
PURPOSE: The FAT1 gene is involved in some cancers; however, its role in medulloblastoma is less clear. This study investigated the effects of FAT1 expression on the prognosis of medulloblastoma patients. METHODS: Whole exome sequencing was undertaken in 40 medulloblastoma patient samples. FAT1 mRNA and protein expression levels in normal and brain tumor tissues were determined by fluorescence quantitative PCR and immunohistochemistry, respectively. The association of FAT1 expression with overall survival (OS) was examined by Kaplan-Meier curve analysis with a log-rank test...
November 8, 2016: Tumori
https://www.readbyqxmd.com/read/27811057/elp3-links-trna-modification-to-ires-dependent-translation-of-lef1-to-sustain-metastasis-in-breast-cancer
#7
Sylvain Delaunay, Francesca Rapino, Lars Tharun, Zhaoli Zhou, Lukas Heukamp, Martin Termathe, Kateryna Shostak, Iva Klevernic, Alexandra Florin, Hadrien Desmecht, Christophe J Desmet, Laurent Nguyen, Sebastian A Leidel, Anne E Willis, Reinhard Büttner, Alain Chariot, Pierre Close
Quantitative and qualitative changes in mRNA translation occur in tumor cells and support cancer progression and metastasis. Posttranscriptional modifications of transfer RNAs (tRNAs) at the wobble uridine 34 (U34) base are highly conserved and contribute to translation fidelity. Here, we show that ELP3 and CTU1/2, partner enzymes in U34 mcm(5)s(2)-tRNA modification, are up-regulated in human breast cancers and sustain metastasis. Elp3 genetic ablation strongly impaired invasion and metastasis formation in the PyMT model of invasive breast cancer...
October 17, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27801482/expression-of-myogenes-in-longissimus-dorsi-muscle-during-prenatal-development-in-commercial-and-local-piau-pigs
#8
Evelyze Pinheiro Dos Reis, Débora Martins Paixão, Otávio José Bernardes Brustolini, Fabyano Fonseca E Silva, Walmir Silva, Flávio Marcos Gomes de Araújo, Anna Christina de Matos Salim, Guilherme Oliveira, Simone Eliza Facioni Guimarães
This study used qRT-PCR to examine variation in the expression of 13 myogenes during muscle development in four prenatal periods (21, 40, 70 and 90 days post-insemination) in commercial (the three-way Duroc, Landrace and Large-White cross) and local Piau pig breeds that differ in muscle mass. There was no variation in the expression of the CHD8, EID2B, HIF1AN, IKBKB, RSPO3, SOX7 and SUFU genes at the various prenatal ages or between breeds. The MAP2K1 and RBM24 genes showed similar expression between commercial and Piau pigs but greater expression (p < 0...
October 2016: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/27793772/tcf7l2-mediates-the-cellular-and-behavioral-response-to-chronic-lithium-treatment-in-animal-models
#9
Katarzyna Misztal, Nikola Brozko, Andrzej Nagalski, Lukasz M Szewczyk, Marta Krolak, Katarzyna Brzozowska, Jacek Kuznicki, Marta B Wisniewska
The mechanism of lithium's therapeutic action remains obscure, hindering the discovery of safer treatments for bipolar disorder. Lithium can act as an inhibitor of the kinase GSK3α/β, which in turn negatively regulates β-catenin, a co-activator of LEF1/TCF transcription factors. However, unclear is whether therapeutic levels of lithium activate β-catenin in the brain, and whether this activation could have a therapeutic significance. To address this issue we chronically treated mice with lithium. Although the level of non-phospho-β-catenin increased in all of the brain areas examined, β-catenin translocated into cellular nuclei only in the thalamus...
October 25, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27766950/cyclin-d1-as-a-therapeutic-target-of-renal-cell-carcinoma-a-combined-transcriptomics-tissue-microarray-and-molecular-docking-study-from-the-kingdom-of-saudi-arabia
#10
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
https://www.readbyqxmd.com/read/27766528/wnt-signaling-inhibitor-fh535-selectively-inhibits-cell-proliferation-and-potentiates-imatinib-induced-apoptosis-in-myeloid-leukemia-cell-lines
#11
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
https://www.readbyqxmd.com/read/27764755/icariin-promotes-osteogenic-differentiation-of-rat-bone-marrow-stromal-cells-by-activating-the-er%C3%AE-wnt-%C3%AE-catenin-signaling-pathway
#12
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
https://www.readbyqxmd.com/read/27760204/fine-tuning-of-the-kaposi-s-sarcoma-associated-herpesvirus-life-cycle-in-neighboring-cells-through-the-rta-jag1-notch-pathway
#13
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
https://www.readbyqxmd.com/read/27737314/analyzing-gene-expression-profiles-in-dilated-cardiomyopathy-via-bioinformatics-methods
#14
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
https://www.readbyqxmd.com/read/27716141/multi-omics-analysis-reveals-regulators-of-the-response-to-pdgf-bb-treatment-in-pulmonary-artery-smooth-muscle-cells
#15
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
https://www.readbyqxmd.com/read/27693749/wnt-signaling-promotes-hindgut-fate-commitment-through-regulating-multi-lineage-genes-during-hesc-differentiation
#16
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
https://www.readbyqxmd.com/read/27613243/crucial-genes-associated-with-diabetic-nephropathy-explored-by-microarray-analysis
#17
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
https://www.readbyqxmd.com/read/27595937/smad4-suppresses-the-tumorigenesis-and-aggressiveness-of-neuroblastoma-through-repressing-the-expression-of-heparanase
#18
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
https://www.readbyqxmd.com/read/27586853/grhl3-modulates-epithelial-structure-formation-of-the-circumvallate-papilla-during-mouse-development
#19
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
https://www.readbyqxmd.com/read/27586466/evaluation-of-expression-of-the-wnt-signaling-components-in-canine-mammary-tumors-by-rt%C3%A2-profiler-pcr-array-and-immunochemistry
#20
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
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