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https://www.readbyqxmd.com/read/28087388/unravelling-the-role-of-fatty-acid-metabolism-in-cancer-through-the-foxo3-foxm1-axis
#1
Paula Saavedra-García, Katie Nichols, Zimam Mahmud, Lavender Yuen-Nam Fan, Eric W-F Lam
Obesity and cachexia represent divergent states of nutritional and metabolic imbalance but both are intimately linked to cancer. There is an extensive overlap in their signalling pathways and molecular components involved such as fatty acids (FAs), which likely play a crucial role in cancer. Forkhead box (FOX) proteins are responsible of a wide range of transcriptional programmes during normal development, and the FOXO3-FOXM1 axis is associated with cancer initiation, progression and drug resistance. Free fatty acids (FFAs), FA synthesis and β-oxidation are associated with cancer development and progression...
January 10, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28078605/transcriptional-regulatory-network-analysis-for-gastric-cancer-based-on-mrna-microarray
#2
Yan Wang
We aimed to screen the differential expressed genes (DEGs) and transcriptional factors (TFs) related to gastric cancer. GSE19826 microarray data downloaded from Gene Expression Omnibus was used to identify the differentially expressed genes (DEGs) and PPI network of DEGs were constructed by the Retrieval of Interacting Genes database. Pathway enrichment analysis of DEGs were performed by Gene Set Enrichment Analysis. Then, the transcriptional regulatory network was constructed based on TRANSFAC database. Finally, regulatory impact factor (RIF) of TF was calculated...
January 11, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28075524/topk-t-lak-cell-originated-protein-kinase-inhibitor-exhibits-growth-suppressive-effect-on-small-cell-lung-cancer
#3
Jae-Hyun Park, Hiroyuki Inoue, Taigo Kato, Makda Zewde, Takashi Miyamoto, Yo Matsuo, Ravi Salgia, Yusuke Nakamura
T-lymphokine-activated killer cell-originated protein kinase (TOPK) plays critical roles in cancer cell proliferation as well as maintenance of cancer stem cells (CSC). Small cell lung cancer (SCLC) has highly aggressive phenotype, reveals early spread to distant sites, and results in dismal prognosis with little effective treatment. In this study, we demonstrate that TOPK expression was highly upregulated in both SCLC cell lines and primary tumors. Similar to siRNA-mediated TOPK knockdown effects, treatment with a potent TOPK inhibitor, OTS514, effectively suppressed growth of SCLC cell lines (IC50 ; 0...
January 11, 2017: Cancer Science
https://www.readbyqxmd.com/read/28072973/-expression-of-foxm1-and-bcrp-in-invasive-breast-carcinoma-of-no-special-type-and-its-prognosis-significance
#4
Y Liu, Y P Liu, J Y Liu, H C Yang, Z D Wang
Objective: To investigate the relationship between expression of FoxM1 and BCRP in invasive breast carcinoma of no special type (IBC-NST) tissues and the clinical pathological characteristics and prognosis of the patients. Methods: Seventy-eight cases of IBC-NST with excision were included. The expression of FoxM1 and BCRP was assessed by immunohistochemistry and its relationship with the clinical pathological characteristics and prognosis was evaluated. Results: FoxM1 was expressed in 71.8%(56/78) of IBC-NST, and the expression was related to tumor diameter, TNM staging, ER, PR and HER2...
January 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28061449/central-spindle-proteins-and-mitotic-kinesins-are-direct-transcriptional-targets-of-muvb-b-myb-and-foxm1-in-breast-cancer-cell-lines-and-are-potential-targets-for-therapy
#5
Patrick Wolter, Steffen Hanselmann, Grit Pattschull, Eva Schruf, Stefan Gaubatz
The MuvB multiprotein complex, together with B-MYB and FOXM1 (MMB-FOXM1), plays an essential role in cell cycle progression by regulating the transcription of genes required for mitosis and cytokinesis. In many tumors, B-MYB and FOXM1 are overexpressed as part of the proliferation signature. However, the transcriptional targets that are important for oncogenesis have not been identified. Given that mitotic kinesins are highly expressed in cancer cells and that selected kinesins have been reported as target genes of MMB-FOXM1, we sought to determine which mitotic kinesins are directly regulated by MMB-FOXM1...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28051999/foxm1-evokes-5-fluorouracil-resistance-in-colorectal-cancer-depending-on-abcc10
#6
Tao Xie, Jian Geng, Ye Wang, Liya Wang, Mengxi Huang, Jing Chen, Kai Zhang, Lijun Xue, Xiaobei Liu, Xiaobei Mao, Yanan Chen, Qian Wang, Tingting Dai, Lili Ren, Hongju Yu, Rui Wang, Longbang Chen, Cheng Chen, Xiaoyuan Chu
5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent for colorectal cancer (CRC). However, frequently occurred 5-FU resistance poses a great challenge in the clinic. Elucidating the underlying mechanisms and developing effective strategies against 5-FU resistance are highly desired. Here we identified the upregulation of FOXM1 in 5-FU nonresponsive CRC patients by gene expression profile analysis and 5-FU-resistant CRC cells by qRT-PCR assay. Silencing of FOXM1 promoted the sensitivity of CRC cells to 5-FU by enhancing cell apoptosis, while overexpression of FOXM1 conferred CRC cells with 5-FU resistance both in vitro and in vivo...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28012972/a-novel-peptide-9r-p201-strongly-inhibits-the-viability-proliferation-and-migration-of-liver-cancer-hepg2-cells-and-induces-apoptosis-by-down-regulation-of-foxm1-expression
#7
Zhenfei Bi, Wenrong Liu, Ruofang Ding, Yiran Wu, Rongkun Dou, Wenwen Zhang, Xue Yuan, Xinrong Liu, Lili Xiong, Zhiyun Guo, Canquan Mao
Overexpression of FoxM1 was closely related to the proliferation, metastasis, chemo-resistance and poor prognosis of various cancers. FoxM1 was regarded as the Achilles' heel of cancer and a potential target for anti-cancer drug discovery. We previously obtained several high affinity peptides from the phage random library against the DNA binding domain of FoxM1c (FoxM1c-DBD) protein. Here in this paper, we found that 9R-P201, one of the novel peptides, showed stronger inhibition to HepG2 cancer cells than those of DU145, HUVEC and L-02 cells with an IC50 of 43...
December 21, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28011860/reprogramming-derived-gene-cocktail-increases-cardiomyocyte-proliferation-for-heart-regeneration
#8
Yuan-Yuan Cheng, Yu-Ting Yan, David J Lundy, Annie Ha Lo, Yu-Ping Wang, Shu-Chian Ruan, Po-Ju Lin, Patrick Ch Hsieh
Although remnant cardiomyocytes (CMs) possess a certain degree of proliferative ability, efficiency is too low for cardiac regeneration after injury. In this study, we identified a distinct stage within the initiation phase of CM reprogramming before the MET process, and microarray analysis revealed the strong up-regulation of several mitosis-related genes at this stage of reprogramming. Several candidate genes were selected and tested for their ability to induce CM proliferation. Delivering a cocktail of three genes, FoxM1, Id1, and Jnk3-shRNA (FIJs), induced CMs to re-enter the cell cycle and complete mitosis and cytokinesis in vitro More importantly, this gene cocktail increased CM proliferation in vivo and significantly improved cardiac function and reduced fibrosis after myocardial infarction...
December 23, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28002884/increased-foxm1-expression-is-associated-with-clinicopathological-features-and-confers-a-poor-prognosis-in-human-hepatocellular-carcinoma
#9
Mayumi Egawa, Yuichi Yoshida, Satoshi Ogura, Tomohide Kurahashi, Takashi Kizu, Kunimaro Furuta, Yoshihiro Kamada, Norihiro Chatani, Mina Hamano, Shinichi Kiso, Hayato Hikita, Tomohide Tatsumi, Hidetoshi Eguchi, Hiroaki Nagano, Yuichiro Doki, Masaki Mori, Tetsuo Takehara
AIMS: Forkhead Box M1 (FoxM1) is a proliferation-specific transcription factor. In this study, we aimed to elucidate the clinicopathological and prognostic values of FoxM1expression in human hepatocellular carcinoma (HCC) and correlate FoxM1 expression with various etiologies of liver diseases. We also investigated its therapeutic value in HCC. METHODS: We investigated the expression of FoxM1 in tumor tissues and adjacent non-tumor tissues of 79 Japanese HCC patients by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis...
December 21, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/27998466/-clinical-significance-of-foxm1-and-gli-1-protein-expression-in-high-grade-ovarian-serous-carcinoma
#10
J Zhang, Z Y Li, X J Duan, X M Fan, W N Liu, Y H Li
Objective: To investigate the different expression and prognostic significance of forkhead box M1 (FOXM1) and Gli-l in ovarian high grade serous carcinoma (HGSC). Methods: The expressions of FOXM1 and Gli-1 in 94 cases of HGSC and 20 cases of normal fallopian tube tissues were detected by immunohistochemistry. Kaplan-Meier analysis and Cox multivariate survival analysis were used to assess the relationship of the FOXM1 and Gli-1 levels with age, International Federation of Gynecology and Obstetrics (FIGO) stage, omental metastasis, and residual foci and prognosis of HGSC...
December 23, 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/27923917/metadherin-astrocyte-elevated-gene-1-positively-regulates-the-stability-and-function-of-forkhead-box-m1-during-tumorigenesis
#11
Lixuan Yang, Kejun He, Sheng Yan, Yibing Yang, Xinya Gao, Maolei Zhang, Zhibo Xia, Zhengsong Huang, Suyun Huang, Nu Zhang
BACKGROUND: Forkhead box M1 (FOXM1) is overexpressed and activates numerous oncoproteins in tumors. However, the mechanism by which the FOXM1 protein aberrantly accumulates in human cancer remains uncertain. This study was designed to clarify the upstream signaling pathway(s) that regulate FOXM1 protein stability and transcriptional activity. METHODS: Mass spectrometry and immunoprecipitation were performed to identify the FOXM-metadherin (MTDH) interaction. In vivo and in vitro ubiquitination assays were conducted to test the effect of MTDH on FOXM1 stability...
December 6, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27863397/targeting-gli-by-gant61-involves-mechanisms-dependent-on-inhibition-of-both-transcription-and-dna-licensing
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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