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https://www.readbyqxmd.com/read/28302717/regulatory-signatures-of-liver-regeneration-distilled-by-integrative-analysis-of-mrna-histone-methylation-and-proteomics
#1
Yoshihiro Sato, Yasutake Katoh, Mitsuyo Matsumoto, Masaki Sato, Masayuki Ebina, Ari Itoh-Nakadai, Ryo Funayama, Keiko Nakayama, Michiaki Unno, Kazuhiko Igarashi
The capacity of the liver to regenerate is likely to be encoded as a plasticity of molecular networks within the liver. By applying a combination of comprehensive analyses of the epigenome, transcriptome and proteome, we herein depict the molecular landscape of liver regeneration. We demonstrated that histone H3K4 was tri-methylated at the promoter regions of many loci, among which only a fraction including cell-cycle-related genes were transcriptionally up-regulated. A cistrome analysis guided by the histone methylation patterns and the transcriptome identified FOXM1 as the key transcription factor promoting liver regeneration, which was confirmed in vitro using a hepatocarcinoma cell line...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28289076/fumarate-mediates-a-chronic-proliferative-signal-in-fumarate-hydratase-inactivated-cancer-cells-by-increasing-transcription-and-translation-of-ferritin-genes
#2
Michael John Kerins, Ajay Vashisht, Benjamin Xi-Tong Liang, Spencer Jordan Duckworth, Brandon John Praslicka, James Akira Wohlschlegel, Aikseng Ooi
Germline mutations of the gene encoding the tricarboxylic acid cycle (TCA cycle) enzyme, fumarate hydratase (FH), cause a hereditary cancer syndrome known as hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC associated tumors harbor biallelic FH inactivation that results in the accumulation of the TCA cycle metabolite, fumarate. Although it is known that the fumarate accumulation can alter cellular signaling, if and how fumarate confers a growth advantage remains unclear. Here we show that fumarate accumulation confers a chronic proliferative signal by disrupting cellular iron signaling...
March 13, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28286049/insulin-signaling-regulates-the-foxm1-plk1-cenp-a-pathway-to-promote-adaptive-pancreatic-%C3%AE-%C3%A2-cell-proliferation
#3
Jun Shirakawa, Megan Fernandez, Tomozumi Takatani, Abdelfattah El Ouaamari, Prapaporn Jungtrakoon, Erin R Okawa, Wei Zhang, Peng Yi, Alessandro Doria, Rohit N Kulkarni
Investigation of cell-cycle kinetics in mammalian pancreatic β cells has mostly focused on transition from the quiescent (G0) to G1 phase. Here, we report that centromere protein A (CENP-A), which is required for chromosome segregation during the M-phase, is necessary for adaptive β cell proliferation. Receptor-mediated insulin signaling promotes DNA-binding activity of FoxM1 to regulate expression of CENP-A and polo-like kinase-1 (PLK1) by modulating cyclin-dependent kinase-1/2. CENP-A deposition at the centromere is augmented by PLK1 to promote mitosis, while knocking down CENP-A limits β cell proliferation and survival...
February 26, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28281307/integrated-expression-analysis-identifies-transcription-networks-in-mouse-and-human-gastric-neoplasia
#4
Zheng Chen, Mohammed Soutto, Bushra Rahman, Muhammad W Fazili, DunFa Peng, Maria Blanca Piazuelo, Heidi Chen, M Kay Washington, Yu Shyr, Wael El-Rifai
Gastric cancer is a leading cause of cancer-related deaths worldwide. The Tff1 knockout (KO) mouse model develops gastric lesions that include low-grade dysplasia (LGD), high-grade dysplasia (HGD), and adenocarcinomas. In this study, we used Affymetrix microarrays gene expression platforms for analysis of molecular signatures in the mouse stomach (Tff1-KO (LGD) and Tff1 wild-type (normal)) and human gastric cancer tissues and their adjacent normal tissue samples. Combined integrated bioinformatics analysis of mouse and human datasets indicated that 172 genes were consistently deregulated in both human gastric cancer samples and Tff1-KO LGD lesions (P<0...
March 9, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28277541/the-foxm1-abcc5-axis-contributes-to-paclitaxel-resistance-in-nasopharyngeal-carcinoma-cells
#5
Youxiang Hou, Qianling Zhu, Zheng Li, Yongbo Peng, Xiaohui Yu, Bowen Yuan, Yijun Liu, Youhong Liu, Linglong Yin, Yuchong Peng, Zhenghua Jiang, Jinping Li, Bowen Xie, Yumei Duan, Guolin Tan, Kurban Gulina, Zhicheng Gong, Lunquan Sun, Xuegong Fan, Xiong Li
Paclitaxel is clinically used as a first-line chemotherapeutic regimen for several cancer types, including head and neck cancers. However, acquired drug resistance results in the failure of therapy, metastasis and relapse. The drug efflux mediated by ATP-binding cassette (ABC) transporters and the survival signals activated by forkhead box (FOX) molecules are critical in the development of paclitaxel drug resistance. Whether FOX molecules promote paclitaxel resistance through drug efflux remains unknown. In this study, we developed several types of paclitaxel-resistant (TR) nasopharyngeal carcinoma (NPC) cells...
March 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28276310/basic-transcription-factor-3-is-required-for-proliferation-and-epithelial-mesenchymal-transition-via-regulation-of-foxm1-and-jak2-stat3-signaling-in-gastric-cancer
#6
De-Zhong Zhang, Bing-He Chen, Lan-Fang Zhang, Ming-Kun Cheng, Xiang-Jie Fang, Xin-Jun Wu
Gastric cancer (GC) is the most common epithelial malignancy worldwide. Basic transcription factor 3 (BTF3) plays a crucial role in the regulation of various biological processes. We designed experiments to investigate the molecular mechanism underlying the role of BTF3 in GC cell proliferation and metastasis. We confirmed that BTF3 expression was decreased in GC tissues and several GC cell lines. Lentivirus-mediated downregualtion of BTF3 reduced cell proliferation, induced S and G2/M cell cycle arrest, and increased apoptosis...
March 8, 2017: Oncology Research
https://www.readbyqxmd.com/read/28275791/-knockdown-of-grb7-inhibits-growth-of-oral-squamous-cell-carcinoma-cell-proliferation-and-promoted-apoptosis-through-erk-foxm1-pathway
#7
Bing-Yao Liu, Gang Cao, Zhen Dong, Wei Chen, Jin-Ke Xu, Sen-Lin Zhang, Zhi-Qiang Weng
PURPOSE: To investigate the effect of growth factor receptor-bound 7 (Grb7) on oral squamous cell carcinoma growth and tumor xenografts. METHODS: Cal27 and hNOK cells were cultivated, real-time PCR and Western blotting were used to detect the expression of Grb7 in hNOK and Cal27. Cal27 was transfected with Grb7 siRNA for 48 h, cell proliferation was assayed using MTT. Flow cytometry was used to determine the cell cycle and apoptosis. Western blot was used to evaluate the expression of caspase3, Bax, bcl-2, Cyclin D1, Rb, E2F1, ERK and FOXM1...
December 2016: Shanghai Kou Qiang Yi Xue, Shanghai Journal of Stomatology
https://www.readbyqxmd.com/read/28266316/genomic-copy-number-variation-associated-with-clinical-outcome-in-canine-cutaneous-mast-cell-tumors
#8
Paulo C Jark, Deborah B P Mundin, Marcio de Carvalho, Raquel B Ferioli, Letícia A Anai, Fabio A Marchi, Silvia R Rogatto, Renee Laufer-Amorim, Mirela Tinucci-Costa
Mast cell tumors are the most common malignant cutaneous tumors in dogs. Although there are several prognostic factors involved, the clinical and biological behavior of this type of tumor varies greatly, making the best choice of treatment challenging. Molecular techniques can be used to evaluate a large number of genes involved in the neoplastic process and aid in the selection of candidate genes related to prognostic and predicting factors. Identification of the genes associated with tumor development and progression can be performed through the analysis of numerical and structural changes in DNA isolated from tumor cells by array comparative genomic hybridization (aCGH)...
November 17, 2016: Research in Veterinary Science
https://www.readbyqxmd.com/read/28260073/foxm1-regulates-glycolysis-in-hepatocellular-carcinoma-by-transactivating-glucose-transporter-1-expression
#9
Runze Shang, Meng Pu, Yu Li, Desheng Wang
The Forkhead box M1 (FOXM1) transcription factor plays crucial roles in the initiation and progression of various malignancies, including hepatocellular carcinoma (HCC). However, the mechanism by which FOXM1 regulates cancer metabolism remains unclear. In the present study, overexpression and RNA interference (RNAi) approaches were used to investigate the role of FOXM1 in the regulation of glycolysis in vitro. Luciferase reporter assays were used to explore the transcriptional regulation of the glucose transporter 1 (GLUT1) promoter by FOXM1...
February 22, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28258481/diarylheptanoids-suppress-proliferation-of-pancreatic-cancer-panc-1-cells-through-modulating-shh-gli-foxm1-pathway
#10
Guang-Zhi Dong, Ji Hye Jeong, Yu-Ih Lee, So Yoon Lee, Hui-Yuan Zhao, Raok Jeon, Hwa Jin Lee, Jae-Ha Ryu
Pancreatic cancer is one of the leading causes of cancer, and it has the lowest 5-year survival rates. It is necessary to develop more potent anti-pancreatic cancer drugs to overcome the fast metastasis and resistance to surgery, radiotherapy, chemotherapy, and combinations of these. We have identified several diarylheptanoids as anti-pancreatic cancer agents from Alpinia officinarum (lesser galangal) and Alnus japonica. These diarylheptanoids suppressed cell proliferation and induced the cell cycle arrest of pancreatic cancer cells (PANC-1)...
March 3, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28251397/effect-of-lifelong-football-training-on-the-expression-of-muscle-molecular-markers-involved-in-healthy-longevity
#11
A Mancini, D Vitucci, G Labruna, E Imperlini, M B Randers, J F Schmidt, M Hagman, T R Andersen, R Russo, S Orrù, P Krustrup, F Salvatore, P Buono
PURPOSE: We investigated whether lifelong football training affects the expression of healthy longevity-related muscle molecular markers. METHODS: Biopsies were collected from the vastus lateralis muscle of 10 lifelong football-trained men (68.2 ± 3.0 years) and of 10 active untrained healthy men (66.7 ± 1.3 years). Gene and protein expression was measured by RTqPCR on RNA and by western blotting on protein extracts from muscle biopsies, respectively...
March 1, 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/28249813/induction-of-chromosome-instability-by-activation-of-yes-associated-protein-and-forkhead-box-m1-in-liver-cancer
#12
Sofia M E Weiler, Federico Pinna, Thomas Wolf, Teresa Lutz, Aman Geldiyev, Carsten Sticht, Maria Knaub, Stefan Thomann, Michaela Bissinger, Shan Wan, Stephanie Rössler, Diana Becker, Norbert Gretz, Hauke Lang, Frank Bergmann, Vladimir Ustiyan, Tatiana V Kalin, Stephan Singer, Ju-Seog Lee, Jens U Marquardt, Peter Schirmacher, Vladimir V Kalinichenko, Kai Breuhahn
BACKGROUND & AIMS: Many different types of cancer cells have chromosome instability. The hippo pathway leads to phosphorylation of the transcriptional activator yes associated protein 1 (YAP1, YAP), which regulates proliferation and has been associated with development of liver cancer. We investigated the effects of hippo signaling via YAP on chromosome stability and hepatocarcinogenesis in humans and mice. METHODS: We analyzed transcriptome data from 242 patients with hepatocellular carcinoma (HCC) to search for gene signatures associated with chromosomal instability; we investigated associations with overall survival time and cancer recurrence using Kaplan-Meier curves...
February 26, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28225180/microrna-216b-inhibits-cell-proliferation-and-migration-in-human-melanoma-by-targeting-foxm1-in-vitro-and-in-vivo
#13
Mengyao Sun, Xiaopeng Wang, Chen Tu, Shuang Wang, Jianqiang Qu, Shengxiang Xiao
MicroRNAs (miRNAs) play an increasingly important role in cancer growth by coordinately suppressing genes that controlcell migration, proliferationand invasion. The above results can be achieved through the regulation of gene expression by miRNAs bysuppressing translation or the directsequence-specific degradation of the targetedmRNA. In the present study, we indicate that the expression of miR-216b could be effectively repressed both in human melanoma tissues through a comparison with primary melanoma and in human melanoma cell lines through a comparison with a normal human keratinocyte line...
February 22, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28199985/foxm1-promotes-the-progression-of-prostate-cancer-by-regulating-psa-gene-transcription
#14
Youhong Liu, Yijun Liu, Bowen Yuan, Linglong Yin, Yuchong Peng, Xiaohui Yu, Weibing Zhou, Zhicheng Gong, Jianye Liu, Leye He, Xiong Li
Androgen/AR is the primary contributor to prostate cancer (PCa) progression by regulating Prostate Specific Antigen (PSA) gene transcription. The disease inevitably evolves to androgen-independent (AI) status. Other mechanisms by which PSA is regulated and develops to AI have not yet been fully determined. FOXM1 is a cell proliferation-specific transcription factor highly expressed in PCa cells compared to non-malignant prostate epithelial cells, suggesting that the aberrant overexpression of FOXM1 contributes to PCa development...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28195122/integrated-genomic-analyses-of-de-novo-pathways-underlying-atypical-meningiomas
#15
Akdes Serin Harmancı, Mark W Youngblood, Victoria E Clark, Süleyman Coşkun, Octavian Henegariu, Daniel Duran, E Zeynep Erson-Omay, Leon D Kaulen, Tong Ihn Lee, Brian J Abraham, Matthias Simon, Boris Krischek, Marco Timmer, Roland Goldbrunner, S Bülent Omay, Jacob Baranoski, Burçin Baran, Geneive Carrión-Grant, Hanwen Bai, Ketu Mishra-Gorur, Johannes Schramm, Jennifer Moliterno, Alexander O Vortmeyer, Kaya Bilgüvar, Katsuhito Yasuno, Richard A Young, Murat Günel
Meningiomas are mostly benign brain tumours, with a potential for becoming atypical or malignant. On the basis of comprehensive genomic, transcriptomic and epigenomic analyses, we compared benign meningiomas to atypical ones. Here, we show that the majority of primary (de novo) atypical meningiomas display loss of NF2, which co-occurs either with genomic instability or recurrent SMARCB1 mutations. These tumours harbour increased H3K27me3 signal and a hypermethylated phenotype, mainly occupying the polycomb repressive complex 2 (PRC2) binding sites in human embryonic stem cells, thereby phenocopying a more primitive cellular state...
February 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28188776/aurora-a-overexpression-aurka-is-driven-by-foxm1-and-mapk-erk-activation-in-melanoma-cells-harbouring-braf-or-nras-mutations-impact-on-melanoma-prognosis-and-therapy
#16
Joan Anton Puig-Butille, Antònia Vinyals, Josep R Ferreres, Paula Aguilera, Eduard Cabré, Gemma Tell-Martí, Joaquim Marcoval, Francesca Mateo, Luís Palomero, Celia Badenas, Josep M Piulats, Josep Malvehy, Miquel A Pujana, Susana Puig, Àngels Fabra
The cell cycle-related genes AURORA A and Forkhead box M1 (FOXM1) are overexpressed in melanoma. We show here that AURKA overexpression is associated with poor prognosis in three independent cohorts of melanoma patients and correlates with the presence of genomic amplification of AURKA locus and BRAF(V600E) mutation. AURKA overexpression may also be driven to increased promoter activation through elements such as ETS and FOXM1 found within the 5' proximal promoter region. Activated MAPK-ERK signalling pathway mediates robust AURKA promoter activation, thereby knockdown of BRAF(V600E) and ERK inhibition results in reduced AURKA transcription and expression...
February 7, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28187446/targeting-of-apoptotic-pathways-by-smac-or-bh3-mimetics-distinctly-sensitizes-paclitaxel-resistant-triple-negative-breast-cancer-cells
#17
Effrosini G Panayotopoulou, Anna-Katharina Müller, Melanie Börries, Hauke Busch, Guohong Hu, Sima Lev
Standard chemotherapy is the only systemic treatment for triple-negative breast cancer (TNBC), and despite the good initial response, resistance remains a major therapeutic obstacle. Here, we employed a High-Throughput Screen to identify targeted therapies that overcome chemoresistance in TNBC. We applied short-term paclitaxel treatment and screened 320 small-molecule inhibitors of known targets to identify drugs that preferentially and efficiently target paclitaxel-treated TNBC cells. Among these compounds the SMAC mimetics (BV6, Birinapant) and BH3-mimetics (ABT-737/263) were recognized as potent targeted therapy for multiple paclitaxel-residual TNBC cell lines...
February 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28187428/a-novel-integrative-risk-index-of-papillary-thyroid-cancer-progression-combining-genomic-alterations-and-clinical-factors
#18
Qing Cheng, Xuechan Li, Chaitanya R Acharya, Terry Hyslop, Julie Ann Sosa
Although the majority of papillary thyroid cancer (PTC) is indolent, a subset of PTC behaves aggressively despite the best available treatment. A major clinical challenge is to reliably distinguish early on between those patients who need aggressive treatment from those who do not. Using a large cohort of PTC samples obtained from The Cancer Genome Atlas (TCGA), we analyzed the association between disease progression and multiple forms of genomic data, such as transcriptome, somatic mutations, and somatic copy number alterations, and found that genes related to FOXM1 signaling pathway were significantly associated with PTC progression...
February 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28185110/foxm1-mediated-rfc5-expression-promotes-temozolomide-resistance
#19
Wan-Xin Peng, Xiu Han, Chun-Li Zhang, Lu Ge, Feng-Yi Du, Jie Jin, Ai-Hua Gong
Although methylguanine-DNA-methyltransferase (MGMT) plays an important role in resistance to temozolomide (TMZ) in glioma, 40% of gliomas with MGMT inactivation are still resistant to TMZ. The underlying mechanism is not clear. Here, we report that forkhead box M1 (FoxM1) transcriptionally activates the expression of DNA repair gene replication factor C5 (RFC5) to promote TMZ resistance in glioma cells independent of MGMT activation. We showed that RFC5 expression is positively correlated with FoxM1 expression in human glioma cells and FoxM1 is able to transcriptionally activate RFC expression by interaction with the RFC5 promoter...
February 9, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28184921/tanshinone%C3%A2-iia-suppresses-gastric-cancer-cell-proliferation-and-migration-by-downregulation-of-foxm1
#20
Jiao Yu, Xiaoxia Wang, Yuhua Li, Bin Tang
Tanshinone IIA (TSN) exhibits a variety of anticancer effects. However, whether it inhibits gastric cancer (GC) cell proliferation and migration and the mechanism remain unclear. In the present study, different concentrations of TSN were co-incubated with SGC-7901 cells. The pcDNA-FOXM1 or FOXM1-siRNA plasmid was transfected into cells before treatment with 5 µg/l TSN. The proliferation and migration abilities of the SGC-7901 cells were tested by MTT and wound healing assays. Western blotting was used to investigate the expression levels of P21, Ki-67, PCNA, MMP-2, MMP-9 and FOXM1...
March 2017: Oncology Reports
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