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https://www.readbyqxmd.com/read/27863397/targeting-gli-by-gant61-involves-mechanisms-dependent-on-inhibition-of-both-transcription-and-dna-licensing
#1
Ruowen Zhang, Jiahui Wu, Sylvain Ferrandon, Katie J Glowacki, Janet A Houghton
The GLI genes are transcription factors and in cancers are oncogenes, aberrantly and constitutively activated. GANT61, a specific GLI inhibitor, has induced extensive cytotoxicity in human models of colon cancer. The FOXM1 promoter was determined to be a transcriptional target of GLI1. In HT29 cells, inhibition of GLI1 binding at the GLI consensus sequence by GANT61 led to inhibited binding of Pol II, the pause-release factors DSIF, NELF and p-TEFb. The formation of R-loops (RNA:DNA hybrids, ssDNA), were reduced by GANT61 at the FOXM1 promoter...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27863385/gli1-promotes-colorectal-cancer-metastasis-in-a-foxm1-dependent-manner-by-activating-emt-and-pi3k-akt-signaling
#2
Chuan Zhang, Yong Wang, YiFei Feng, Yue Zhang, Bing Ji, Sen Wang, Ye Sun, Chunyan Zhu, Dongsheng Zhang, Yueming Sun
Colorectal cancer(CRC) is one of the most commonly diagnosed cancers in human beings and metastasis is the main death reason. Recently, Gli1 has been reported to be a key regulator of various cancer biologies and genes expressions. However, the detailed molecular mechanism of Gli1 in CRC metastasis remains largely unknown. In this study, we aimed to investigate the role of Gli1 in CRC metastasis. We used qRT-PCR, Immunohistochemistry and Western blot to test the expression levels of Gli1, Foxm1 and other target genes in the tissues and cells; Lentivirus stable transfection to change the expression levels of Gli1 and Foxm1; Wound-healing, cell invasion, migration assays and tail vein metastatic assay to test the role of Gli1 in CRC metastasis in vitro and vivo...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27852048/igfbp2-expression-predicts-idh-mutant-glioma-patient-survival
#3
L Eric Huang, Adam L Cohen, Howard Colman, Randy L Jensen, Daniel W Fults, William T Couldwell
Mutations of the isocitrate dehydrogenase (IDH) 1 and 2 genes occur in ~80% of lower-grade (WHO grade II and grade III) gliomas. Mutant IDH produces (R)-2-hydroxyglutarate, which induces DNA hypermethylation and presumably drives tumorigenesis. Interestingly, IDH mutations are associated with improved survival in glioma patients, but the underlying mechanism for the difference in survival remains unclear. Through comparative analyses of 286 cases of IDH-wildtype and IDH-mutant lower-grade glioma from a TCGA data set, we report that IDH-mutant gliomas have increased expression of tumor-suppressor genes (NF1, PTEN, and PIK3R1) and decreased expression of oncogenes(AKT2, ARAF, ERBB2, FGFR3, and PDGFRB) and glioma progression genes (FOXM1, IGFBP2, and WWTR1) compared with IDH-wildtype gliomas...
November 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27845446/chromatin-associated-setd3-negatively-regulates-vegf-expression
#4
Ofir Cohn, Michal Feldman, Lital Weil, Margarita Kublanovsky, Dan Levy
SETD3 is a member of the protein lysine methyltransferase (PKMT) family, which catalyzes the addition of methyl group to lysine residues. Accumulating data suggest that PKMTs are involved in the regulation of a broad spectrum of biological processes by targeting histone and non-histone proteins. Using a proteomic approach, we have identified 172 new SETD3 interacting proteins. We show that SETD3 binds and methylates the transcription factor FoxM1, which has been previously shown to be associated with the regulation of VEGF expression...
November 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27812538/proproliferative-and-antiapoptotic-action-of-exogenously-introduced-yap-in-pancreatic-%C3%AE-cells
#5
Ting Yuan, Sahar Rafizadeh, Zahra Azizi, Blaz Lupse, Kanaka Durga Devi Gorrepati, Sushil Awal, Jose Oberholzer, Kathrin Maedler, Amin Ardestani
Loss of functional pancreatic β cells is a hallmark of both type 1 and 2 diabetes. Identifying the pathways that promote β cell proliferation and/or block β cell apoptosis is a potential strategy for diabetes therapy. The transcriptional coactivator Yes-associated protein (YAP), a major downstream effector of the Hippo signaling pathway, is a key regulator of organ size and tissue homeostasis by modulating cell proliferation and apoptosis. YAP is not expressed in mature primary human and mouse β cells. We aimed to identify whether reexpression of a constitutively active form of YAP promotes β cell proliferation/survival...
November 3, 2016: JCI Insight
https://www.readbyqxmd.com/read/27764801/foxm1-and-stat3-interaction-confers-radioresistance-in-glioblastoma-cells
#6
Uday B Maachani, Uma Shankavaram, Tamalee Kramp, Philip J Tofilon, Kevin Camphausen, Anita T Tandle
Glioblastoma multiforme (GBM) continues to be the most frequently diagnosed and lethal primary brain tumor. Adjuvant chemo-radiotherapy remains the standard of care following surgical resection. In this study, using reverse phase protein arrays (RPPAs), we assessed the biological effects of radiation on signaling pathways to identify potential radiosensitizing molecular targets. We identified subsets of proteins with clearly concordant/discordant behavior between irradiated and non-irradiated GBM cells in vitro and in vivo...
October 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27756785/a-positive-feedback-loop-of-lncrna-pvt1-and-foxm1-facilitates-gastric-cancer-growth-and-invasion
#7
Xiang Du, Mi-Die Xu, Yiqin Wang, Wei-Wei Weng, Ping Wei, Peng Qi, Qiongyan Zhang, Cong Tan, Shujuan Ni, Lei Dong, Yusi Yang, Wanrun Lin, Qinghua Xu, Dan Huang, Zhaohui Huang, Yuqing Ma, Wei Zhang, Weiqi Sheng
PURPOSE: The long noncoding RNA (lncRNA) PVT1 is an important epigenetic regulator with a critical role in human tumors. Here, we aimed to investigate the clinical application and the potential molecular mechanisms of PVT1 in gastric cancer (GC) tumorigenesis and progression. EXPERIMENTAL DESIGN: The expression level of PVT1 was determined by RT-qPCR analysis in 190 pairs of GC tissues and adjacent normal gastric mucosa tissues (ANTs). The biological functions of PVT1 were assessed by in vitro and in vivo functional experiments...
October 18, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27716361/long-non-coding-rna-h19-regulates-foxm1-expression-by-competitively-binding-endogenous-mir-342-3p-in-gallbladder-cancer
#8
Shou-Hua Wang, Fei Ma, Zhao-Hui Tang, Xiao-Cai Wu, Qiang Cai, Ming-Di Zhang, Ming-Zhe Weng, Di Zhou, Jian-Dong Wang, Zhi-Wei Quan
BACKGROUND: Long non-coding RNA (lncRNA) H19 has been reported to involve in many kinds of human cancers and functions as an oncogene. Our previous study found that H19 was over-expressed in gallbladder cancer (GBC) and was shown to promote tumor development in GBC. However, the competing endogenous RNA (ceRNA) regulatory network involving H19 in GBC progression has not been fully elucidated. We aim to detect the role of H19 as a ceRNA in GBC. METHODS AND RESULTS: In this study, the expression of H19 and miR-342-3p were analyzed in 35 GBC tissues and matched normal tissues by using quantitative polymerase chain reaction (qRT-PCR)...
October 3, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27698870/association-of-foxm1-expression-with-tumor-histology-and-prognosis-in-wilms-tumor-potential-for-a-new-prognostic-marker
#9
Nadja Apelt, Jochen Hubertus, Doris Mayr, Norbert Graf, Rhoikos Furtwängler, Dietrich Von Schweinitz, Roland Kappler
Wilms tumor (WT) is the most common pediatric renal malignancy. A recent ontogenic model suggests that undifferentiated tumor state, and hence poor prognosis, in WT is determined by stabilization of β-catenin in the nucleus. Forkhead box M1 (FOXM1) is a downstream component of the Wnt pathway and promotes nuclear localization of β-catenin. As elevation of FOXM1 gene expression is prognostic in various types of malignancy, we hypothesized that high FOXM1 expression in WT is associated with undifferentiated histology and thus poor prognosis...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27698840/association-between-foxm1-and-hedgehog-signaling-pathway-in-human-cervical-carcinoma-by-tissue-microarray-analysis
#10
Hong Chen, Jingjing Wang, Hong Yang, Dan Chen, Panpan Li
Forkhead box M1 (FOXM1) and hedgehog (Hh) signaling pathway are implicated in the formation and development of human tumors, including cervical cancer. Previous studies have indicated that FOXM1 may be a downstream target gene of the Hh signaling pathway, but their association in cervical cancer is largely unknown. In the present study, the expression of FOXM1 and Hh signaling molecules was evaluated by immunohistochemical analysis in a tissue microarray that contained 70 cervical cancer tissues and 10 normal cervical tissues...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27698811/expression-of-foxm1-and-the-emt-associated-protein-e-cadherin-in-gastric-cancer-and-its-clinical-significance
#11
Jing Zhang, Xiao-Yu Chen, Ke-Jian Huang, Wei-Dong Wu, Tao Jiang, Jun Cao, Li-Sheng Zhou, Zheng-Jun Qiu, Chen Huang
The aim of the present study was to investigate the expression of forkhead box M1 (FoxM1) and E-cadherin in tissues of gastric cancer in order to reveal any correlation between FoxM1, E-cadherin and clinicopathological parameters. The association between FoxM1 and E-cadherin in the development and progression of gastric cancer was also investigated. The expression of FoxM1 and E-cadherin in gastric cancer and adjacent normal tissue on tissue microarray was detected using immunohistochemistry. The clinicopathological significance of FoxM1 and E-cadherin in gastric cancer was explored, and the association between FoxM1 and E-cadherin was further examined using statistical techniques...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27698803/expression-and-potential-correlation-among-forkhead-box-protein-m1-caveolin-1-and-e-cadherin-in-colorectal-cancer
#12
Jing Zhang, Kundong Zhang, Lisheng Zhou, Weidong Wu, Tao Jiang, Jun Cao, Kejian Huang, Zhengjun Qiu, Chen Huang
The aim of the present study was to investigate the expression and functions of Forkhead box protein M1 (FoxM1), Caveolin-1 (Cav-1) and E-cadherin in colorectal cancer (CRC), and to determine the correlations among these proteins in CRC development and progression. The protein expression of FoxM1, Cav-1 and E-cadherin was identified using a human CRC and normal tissue microarray. A standard immunohistochemistry assay was performed employing anti-FoxM1, anti-Cav-1 and anti-E-cadherin antibodies. The clinicopathological significance of FoxM1, Cav-1 and E-cadherin in CRC was determined, and correlations were investigated between FoxM1 and Cav-1, FoxM1 and E-cadherin, Cav-1 and E-cadherin, respectively...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27694928/nuclear-foxm1-drives-chemoresistance-in-aml
#13
I Khan, M Halasi, M F Zia, P Gann, S Gaitonde, N Mahmud, A L Gartel
No abstract text is available yet for this article.
October 21, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27693640/melk-is-an-oncogenic-kinase-essential-for-early-hepatocellular-carcinoma-recurrence
#14
Hongping Xia, Shik Nie Kong, Jianxiang Chen, Ming Shi, Karthik Sekar, Veerabrahma Pratap Seshachalam, Muthukumar Rajasekaran, Brian Kim Poh Goh, London Lucien Ooi, Kam M Hui
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Many kinases have been found to be intimately involved in oncogenesis and the deregulation of kinase function has emerged as a major mechanism by which cancer cells evade normal physiological constraints on growth and survival. Previously, we have performed gene expression profile analysis on HCC samples and have identified a host of kinases that are remarkably overexpressed in HCC. Among these, the Maternal Embryonic Leucine Zipper Kinase (MELK) is highly overexpressed in HCC and its overexpression strongly correlates with early recurrence and poor patients' survival...
September 28, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27684411/oncogenic-actions-of-skp2-involves-deregulation-of-cdk1-turnover-mediated-by-foxm1
#15
Anand Krishnan, Dhanya K, Saneesh Babu P S, Sankar Jagadeeshan, Manu Prasad, S Asha Nair
Cyclin-dependent kinases (cdks) are central catalytic units of cell division cycle. Among the cdk family members, cdk1 has critical roles in multiple phases of the cell cycle. Aberrant expression or hyper-actions of cdk1 are tumorigenic and yet the complex oncogenic network that regulates its turnover is poorly understood. We found a hitherto unexplored functional connection between skp2 and cdk1 turn over. In vitro knockdown or overexpression of skp2 in cultured cells reduced or induced cdk1 expression indicating skp2 as a positive driver for cdk1...
September 29, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27612430/restoring-mir122-in-human-stem-like-hepatocarcinoma-cells-prompts-tumor-dormancy-through-smad-independent-tgf-%C3%AE-pathway
#16
Loreto Boix, Juan Manuel López-Oliva, Ana Carolina Rhodes, Jordi Bruix
miR122 is the prevalent miRNA in adult healthy liver and it is responsible for liver stem cell differentiation towards hepatocyte lineage. Its expression is frequently lost in hepatocellular carcinoma (HCC). We studied the effects of restoring miR122 expression in a distinctive cell line derived from human HCC-BCLC9 cells-with a solid stem-like cell profile, high tumor initiating ability and undetectable miR122 expression. We generated a stable BCLC9 cell line that expresses miR122 (BCLC9-miR122). Restitution of miR122 in BCLC9 cells, decreases cell proliferation rate and reduces significantly tumor size in vivo...
September 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27601681/pathological-ace2-to-ace-enzyme-switch-in-the-stressed-heart-is-transcriptionally-controlled-by-the-endothelial-brg1-foxm1-complex
#17
Jin Yang, Xuhui Feng, Qiong Zhou, Wei Cheng, Ching Shang, Pei Han, Chiou-Hong Lin, Huei-Sheng Vincent Chen, Thomas Quertermous, Ching-Pin Chang
Genes encoding angiotensin-converting enzymes (Ace and Ace2) are essential for heart function regulation. Cardiac stress enhances Ace, but suppresses Ace2, expression in the heart, leading to a net production of angiotensin II that promotes cardiac hypertrophy and fibrosis. The regulatory mechanism that underlies the Ace2-to-Ace pathological switch, however, is unknown. Here we report that the Brahma-related gene-1 (Brg1) chromatin remodeler and forkhead box M1 (FoxM1) transcription factor cooperate within cardiac (coronary) endothelial cells of pathologically stressed hearts to trigger the Ace2-to-Ace enzyme switch, angiotensin I-to-II conversion, and cardiac hypertrophy...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27593933/dlx1-acts-as-a-crucial-target-of-foxm1-to-promote-ovarian-cancer-aggressiveness-by-enhancing-tgf-%C3%AE-smad4-signaling
#18
D W Chan, W W Y Hui, J J Wang, M M H Yung, L M N Hui, Y Qin, R R Liang, T H Y Leung, D Xu, K K L Chan, K-M Yao, B K Tsang, H Y S Ngan
Recent evidence from a comprehensive genome analysis and functional studies have revealed that FOXM1 is a crucial metastatic regulator that drives cancer progression. However, the regulatory mechanism by which FOXM1 exerts its metastatic functions in cancer cells remains obscure. Here, we report that DLX1 acts as a FOXM1 downstream target, exerting pro-metastatic function in ovarian cancers. Both FOXM1 isoforms (FOXM1B or FOXM1C) could transcriptionally upregulate DLX1 through two conserved binding sites, located at +61 to +69bp downstream (TFBS1) and -675 to -667bp upstream (TFBS2) of the DLX1 promoter, respectively...
September 5, 2016: Oncogene
https://www.readbyqxmd.com/read/27592001/information-dependent-enrichment-analysis-reveals-time-dependent-transcriptional-regulation-of-the-estrogen-pathway-of-toxicity
#19
Salil N Pendse, Alexandra Maertens, Michael Rosenberg, Dipanwita Roy, Rick A Fasani, Marguerite M Vantangoli, Samantha J Madnick, Kim Boekelheide, Albert J Fornace, Shelly-Ann Odwin, James D Yager, Thomas Hartung, Melvin E Andersen, Patrick D McMullen
The twenty-first century vision for toxicology involves a transition away from high-dose animal studies to in vitro and computational models (NRC in Toxicity testing in the 21st century: a vision and a strategy, The National Academies Press, Washington, DC, 2007). This transition requires mapping pathways of toxicity by understanding how in vitro systems respond to chemical perturbation. Uncovering transcription factors/signaling networks responsible for gene expression patterns is essential for defining pathways of toxicity, and ultimately, for determining the chemical modes of action through which a toxicant acts...
September 3, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27568981/fbxo31-protects-against-genomic-instability-by-capping-foxm1-levels-at-the-g2-m-transition
#20
J M Jeffery, M Kalimutho, P Johansson, D G Cardenas, R Kumar, K K Khanna
F-box proteins in conjunction with Skp1, Cul1 and Rbx1 generate SCF complexes that are responsible for the ubiquitination of proteins, leading to their activation or degradation. Here we show that the F-box protein FBXO31 is required for normal mitotic progression and genome stability due to its role in regulating FOXM1 levels during the G2/M transition. FBXO31-depleted cells undergo a transient delay in mitosis due to an activated spindle checkpoint concomitant with an increase in lagging chromosomes and anaphase bridges...
August 29, 2016: Oncogene
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