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FoxM1 AND MYC

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https://www.readbyqxmd.com/read/27612430/restoring-mir122-in-human-stem-like-hepatocarcinoma-cells-prompts-tumor-dormancy-through-smad-independent-tgf-%C3%AE-pathway
#1
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/27452522/foxm1-allows-human-keratinocytes-to-bypass-the-oncogene-induced-differentiation-checkpoint-in-response-to-gain-of-myc-or-loss-of-p53
#2
R Molinuevo, A Freije, I de Pedro, S W Stoll, J T Elder, A Gandarillas
Tumour suppressor p53 or proto-oncogene MYC is frequently altered in squamous carcinomas, but this is insufficient to drive carcinogenesis. We have shown that overactivation of MYC or loss of p53 via DNA damage triggers an anti-oncogenic differentiation-mitosis checkpoint in human epidermal keratinocytes, resulting in impaired cell division and squamous differentiation. Forkhead box M1 (FOXM1) is a transcription factor recently proposed to govern the expression of a set of mitotic genes. Deregulation of FOXM1 occurs in a wide variety of epithelial malignancies...
July 25, 2016: Oncogene
https://www.readbyqxmd.com/read/27451973/a-novel-slug-containing-negative-feedback-loop-regulates-scf-c-kit-mediated-hematopoietic-stem-cell-self-renewal
#3
Z Zhang, P Zhu, Y Zhou, Y Sheng, Y Hong, D Xiang, Z Qian, J Mosenson, W-S Wu
The SCF/c-Kit pathway has crucial roles in controlling hematopoietic stem cell (HSC) renewal. However, little is known about the intracellular regulation of the SCF/c-Kit pathway in HSCs. We report here that Slug, a zinc-finger transcription repressor, functions as a direct transcriptional repressor of c-Kit in HSCs. Conversely, SCF/c-Kit signaling positively regulates Slug through downstream c-Myc and FoxM1 transcription factors. Intriguingly, c-Kit expression is induced by SCF/c-Kit signaling in Slug-deficient HSCs...
July 25, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27399536/338%C3%A2-molecular-mechanisms-underlying-malignant-progression-of-low-grade-idh1-mutant-meningiomas
#4
Murat Gunel
INTRODUCTION: Gliomas represent ∼80% of malignant brain tumors. The molecular mechanisms underlying the malignant progression of IDH1 mutant low-grade gliomas to high-grade glioblastomas are poorly understood. METHODS: We studied paired tumor samples from 41 patients, comparing higher-grade, progressed samples with their lower-grade counterparts using complementary next-generation genomic approaches. These included whole-exome sequencing and copy number, gene expression, and DNA methylation analyses...
August 2016: Neurosurgery
https://www.readbyqxmd.com/read/26877780/bet-bromodomain-inhibition-as-a-therapeutic-strategy-in-ovarian-cancer-by-downregulating-foxm1
#5
Zhenfeng Zhang, Pengfei Ma, Ying Jing, Ying Yan, Mei-Chun Cai, Meiying Zhang, Shengzhe Zhang, Huixin Peng, Zhi-Liang Ji, Wen Di, Zhenyu Gu, Wei-Qiang Gao, Guanglei Zhuang
Ovarian cancer is responsible for the highest mortality among all gynecologic malignancies, and novel therapies are urgently needed to improve patient outcome. Here we performed an integrative genomic analysis and identified the bromodomain and extraterminal domain (BET) protein BRD4 as a potential therapeutic target in ovarian cancer. Suppression of BRD4 using small-molecule BET inhibitors JQ1 and I-BET151, or dual kinase-bromodomain inhibitor volasertib, led to robust and broad antitumor effects across all subclasses of ovarian cancer...
2016: Theranostics
https://www.readbyqxmd.com/read/26820938/pin1-modulates-chemo-resistance-by-up-regulating-foxm1-and-the-involvements-of-wnt-%C3%AE-catenin-signaling-pathway-in-cervical-cancer
#6
Tao Wang, Zi Liu, Fan Shi, Jiquan Wang
The prolyl isomerase Pin1, which is frequently highly expressed in many different cancers, can directly regulate cell proliferation and the cell cycle. However, the role of Pin1 in chemo-resistance remains to be elucidated in cervical cancer. The purpose of the present study was to investigate the role of Pin1 in the chemo-resistance of cervical cancer. The cisplatin resistance was assessed using the MTT assay. Pin1, FoxM1, β-catenin, Cyclin D1, and c-myc expression levels were detected by RT-qPCR or Western blot...
February 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/26719042/microarray-based-gene-expression-profiling-reveals-genes-and-pathways-involved-in-the-oncogenic-function-of-reg3a-on-pancreatic-cancer-cells
#7
Qianqian Xu, Rong Fu, Guoxiao Yin, Xiulan Liu, Yang Liu, Ming Xiang
We previously reported that regenerating islet-derived protein 3 alpha (REG3A) exacerbates pancreatic malignancies. The mechanism of this effect has not been clearly elucidated. Here we first identified key differentially expressed genes (DEGs) and signal pathways in the pancreatic cancer cell line SW1990, compared to two control cell lines, by microarray analysis. We then identified key genes and pathways regulated by REG3A or the cytokine IL6 in SW1990 cells. Afterwards, these DEGs induced by REG3A or IL6 were subjected to KEGG pathway enrichment analysis and GO function analysis by the DAVID online tool...
March 10, 2016: Gene
https://www.readbyqxmd.com/read/26618343/integrated-genomic-characterization-of-idh1-mutant-glioma-malignant-progression
#8
Hanwen Bai, Akdes Serin Harmancı, E Zeynep Erson-Omay, Jie Li, Süleyman Coşkun, Matthias Simon, Boris Krischek, Koray Özduman, S Bülent Omay, Eric A Sorensen, Şevin Turcan, Mehmet Bakırcığlu, Geneive Carrión-Grant, Phillip B Murray, Victoria E Clark, A Gulhan Ercan-Sencicek, James Knight, Leman Sencar, Selin Altınok, Leon D Kaulen, Burcu Gülez, Marco Timmer, Johannes Schramm, Ketu Mishra-Gorur, Octavian Henegariu, Jennifer Moliterno, Angeliki Louvi, Timothy A Chan, Stacey L Tannheimer, M Necmettin Pamir, Alexander O Vortmeyer, Kaya Bilguvar, Katsuhito Yasuno, Murat Günel
Gliomas represent approximately 30% of all central nervous system tumors and 80% of malignant brain tumors. To understand the molecular mechanisms underlying the malignant progression of low-grade gliomas with mutations in IDH1 (encoding isocitrate dehydrogenase 1), we studied paired tumor samples from 41 patients, comparing higher-grade, progressed samples to their lower-grade counterparts. Integrated genomic analyses, including whole-exome sequencing and copy number, gene expression and DNA methylation profiling, demonstrated nonlinear clonal expansion of the original tumors and identified oncogenic pathways driving progression...
January 2016: Nature Genetics
https://www.readbyqxmd.com/read/26261598/integrated-analysis-of-transcription-factor-microrna-and-lncrna-in-an-animal-model-of-obliterative-bronchiolitis
#9
COMPARATIVE STUDY
Ming Dong, Xin Wang, Hong-Lin Zhao, Xing-Long Chen, Jing-Hua Yuan, Jiu-Yi Guo, Ke-Qiu Li, Guang Li
Obliterative bronchiolitis (OB) is characterized by sub-epithelial inflammatory and fibrotic narrowing of the bronchioles, and it is the predominant factor limiting long-term survival after lung transplantation. To explore molecular mechanism of OB, we investigated the interaction of transcription factor (TF), microRNA, long noncoding RNA (lncRNA), and gene expression in the mice model of OB by integrated analysis of TF array, miRNA microarray, and lncRNA and mRNA microarray. After 28 days of orthotopic tracheal transplantation in mice, 42 TFs were significantly up-regulated in allogeneic graft compared to syngeneic graft; 62 miRNAs including miR-376-5p were up-regulated and 17 miRNAs including miR-338-3p were down-regulated over 2-fold; 137 mRNAs were down-regulated and 129 mRNAs were up-regulated over 2-fold; 234 lncRNAs were up-regulated and 212 lncRNAs were down-regulated over 2-fold in the allogeneic model compared to that in the syngeneic control group...
2015: International Journal of Clinical and Experimental Pathology
https://www.readbyqxmd.com/read/26236688/spontaneous-transformation-of-murine-oviductal-epithelial-cells-a-model-system-to-investigate-the-onset-of-fallopian-derived-tumors
#10
Michael P Endsley, Georgette Moyle-Heyrman, Subbulakshmi Karthikeyan, Daniel D Lantvit, David A Davis, Jian-Jun Wei, Joanna E Burdette
High-grade serous carcinoma (HGSC) is the most lethal ovarian cancer histotype. The fallopian tube secretory epithelial cells (FTSECs) are a proposed progenitor cell type. Genetically altered FTSECs form tumors in mice; however, a spontaneous HGSC model has not been described. Apart from a subpopulation of genetically predisposed women, most women develop ovarian cancer spontaneously, which is associated with aging and lifetime ovulations. A murine oviductal cell line (MOE(LOW)) was developed and continuously passaged in culture to mimic cellular aging (MOE(HIGH))...
2015: Frontiers in Oncology
https://www.readbyqxmd.com/read/25973299/high-level-sae2-promotes-malignant-phenotype-and-predicts-outcome-in-gastric-cancer
#11
Duan-Fang Shao, Xiao-Hong Wang, Zi-Yu Li, Xiao-Fang Xing, Xiao-Jing Cheng, Ting Guo, Hong Du, Ying Hu, Bin Dong, Ning Ding, Lin Li, Shen Li, Qing-Da Li, Xian-Zi Wen, Lian-Hai Zhang, Jia-Fu Ji
BACKGROUND: The SUMO pathway has been shown to play an important role in tumorigenesis. This report analyzed the involvement of the sole SUMO-Activating Enzyme Subunit 2 (SAE2) in human gastric cancer (GC) progression and prognosis. METHODS: Expression of SAE2 was examined by Quantigene Plex, western blotting and immunohistochemistry. The expression of SAE2 and c-MYC were detected in parallel in 276 cases. The molecular mechanisms of SAE2 expression and its effects on cell growth, colony formation, migration and invasion were also explored by CCK8 assay, colony formation experiment, transwell chamber assay with or without matrigel, immunoprecipitation and in vivo tumorigenesis and tumor metastasis...
2015: American Journal of Cancer Research
https://www.readbyqxmd.com/read/25938542/cdc20-maintains-tumor-initiating-cells
#12
Qi Xie, Qiulian Wu, Stephen C Mack, Kailin Yang, Leo Kim, Christopher G Hubert, William A Flavahan, Chengwei Chu, Shideng Bao, Jeremy N Rich
Glioblastoma is the most prevalent and lethal primary intrinsic brain tumor. Glioblastoma displays hierarchical arrangement with a population of self-renewing and tumorigenic glioma tumor initiating cells (TICs), or cancer stem cells. While non-neoplastic neural stem cells are generally quiescent, glioblastoma TICs are often proliferative with mitotic control offering a potential point of fragility. Here, we interrogate the role of cell-division cycle protein 20 (CDC20), an essential activator of anaphase-promoting complex (APC) E3 ubiquitination ligase, in the maintenance of TICs...
May 30, 2015: Oncotarget
https://www.readbyqxmd.com/read/25686834/mir-34a-induces-cellular-senescence-via-modulation-of-telomerase-activity-in-human-hepatocellular-carcinoma-by-targeting-foxm1-c-myc-pathway
#13
Xinsen Xu, Wei Chen, Runchen Miao, Yanyan Zhou, Zhixin Wang, Lingqiang Zhang, Yong Wan, Yafeng Dong, Kai Qu, Chang Liu
Increasing evidence suggests that miRNAs can act as either tumor suppressors or oncogenes in carcinogenesis. In the present study, we identified the role of miR-34a in regulating telomerase activity, with subsequent effect on cellular senescence and viability. We found the higher expression of miR-34a was significantly correlated with the advanced clinicopathologic parameters in hepatocellular carcinoma. Furthermore, tumor tissues of 75 HCC patients demonstrated an inverse correlation between the miR-34a level and telomere indices (telomere length and telomerase activity)...
February 28, 2015: Oncotarget
https://www.readbyqxmd.com/read/25628926/high-level-sae2-promotes-malignant-phenotype-and-predicts-outcome-in-gastric-cancer
#14
Duan-Fang Shao, Xiao-Hong Wang, Zi-Yu Li, Xiao-Fang Xing, Xiao-Jing Cheng, Ting Guo, Hong Du, Ying Hu, Bin Dong, Ning Ding, Lin Li, Shen Li, Qing-Da Li, Xian-Zi Wen, Lian-Hai Zhang, Jia-Fu Ji
BACKGROUND: The SUMO pathway has been shown to play an important role in tumorigenesis. This report analyzed the involvement of the sole SUMO-Activating Enzyme Subunit 2 (SAE2) in human gastric cancer (GC) progression and prognosis. METHODS: Expression of SAE2 was examined by Quantigene Plex, western blotting and immunohistochemistry. The expression of SAE2 and c-MYC were detected in parallel in 276 cases. The molecular mechanisms of SAE2 expression and its effects on cell growth, colony formation, migration and invasion were also explored by CCK8 assay, colony formation experiment, transwell chamber assay with or without matrigel, immunoprecipitation and in vivo tumorigenesis and tumor metastasis...
2015: American Journal of Cancer Research
https://www.readbyqxmd.com/read/25290246/dna-microarray-and-signal-transduction-analysis-in-pulmonary-artery-smooth-muscle-cells-from-heritable-and-idiopathic-pulmonary-arterial-hypertension-subjects
#15
Jun Yu, Jamie Wilson, Linda Taylor, Peter Polgar
Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular smooth muscle contraction and proliferation. Here, we analyze genome-wide mRNA expression in human pulmonary arterial smooth muscle cells (HPASMC) isolated from three control, three hereditary (HPAH), and three idiopathic PAH (IPAH) subjects using the Affymetrix Human Gene ST 1.0 chip. The microarray analysis reveals the expression of 537 genes in HPAH and 1024 genes in IPAH changed compared with control HPASMC. Among those genes, 227 genes show similar directionality of expression in both HPAH and IPAH HPASMC...
March 2015: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/25058891/transcriptome-analysis-in-cardiomyocyte-specific-differentiation-of-murine-embryonic-stem-cells-reveals-transcriptional-regulation-network
#16
Lin Gan, Silke Schwengberg, Bernd Denecke
The differentiation to cardiomyocytes is a prerequisite and an important part of heart development. A good understanding of the complicated cardiomyocyte differentiation process benefits cardiogenesis study. Embryonic stem cells (ESCs), cell lines with infinite ability to proliferate and to be differentiated into all cell types of the adult body, are important research tools for investigation of differentiation and meanwhile good models for developmental research. In the current study, genome-wide gene expression of ESCs is profiled through high throughput platform during cardiomyocyte-specific differentiation and maturation...
September 2014: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/24314213/-effects-of-ag1478-on-the-expression-of-foxm1-gene-via-foxo3a-in-non-small-cell-lung-cancer-cells
#17
Xiao-di Gong, Hai-hua Yuan, Jiong-yi Wang, Yue-hui Guo, Jing Shi, Bin Jiang
OBJECTIVE: To explore the effects of EGFR-TKI AG1478 on the expression of FoxMl and FOXO3a genes in non-small cell cancer (NSCLC) cell lines, and explore the effect on cell proliferation and drug sensitivity to AG1478 after down-regulation of FOXMl and FOXO3a expression by RNAi technique. METHODS: Human lung cancer cells were treated with AG1478 at different concentrations. RT-PCR and Western blot were used to examine the expression of P-EGFR, FOXM1, FOXO3a mRNA and protein...
August 2013: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/24213573/foxm1-transcription-factor-is-required-for-the-initiation-of-lung-tumorigenesis-by-oncogenic-kras-g12d
#18
I-C Wang, V Ustiyan, Y Zhang, Y Cai, T V Kalin, V V Kalinichenko
Lung cancer is the leading cause of deaths in cancer patients in the United States. Identification of new molecular targets is clearly needed to improve therapeutic outcomes of this devastating human disease. Activating mutations in K-Ras oncogene and increased expression of FOXM1 protein are associated with poor prognosis in patients with non-small-cell lung cancer. Transgenic expression of activated Kras(G12D) in mouse respiratory epithelium is sufficient to induce lung adenocarcinomas; however, transcriptional mechanisms regulated by K-Ras during the initiation of lung cancer remain poorly understood...
November 13, 2014: Oncogene
https://www.readbyqxmd.com/read/24130802/identification-of-candidate-b-lymphoma-genes-by-cross-species-gene-expression-profiling
#19
Van S Tompkins, Seong-Su Han, Alicia Olivier, Sergei Syrbu, Thomas Bair, Anna Button, Laura Jacobus, Zebin Wang, Samuel Lifton, Pradip Raychaudhuri, Herbert C Morse, George Weiner, Brian Link, Brian J Smith, Siegfried Janz
Comparative genome-wide expression profiling of malignant tumor counterparts across the human-mouse species barrier has a successful track record as a gene discovery tool in liver, breast, lung, prostate and other cancers, but has been largely neglected in studies on neoplasms of mature B-lymphocytes such as diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL). We used global gene expression profiles of DLBCL-like tumors that arose spontaneously in Myc-transgenic C57BL/6 mice as a phylogenetically conserved filter for analyzing the human DLBCL transcriptome...
2013: PloS One
https://www.readbyqxmd.com/read/23907611/human-mitochondrial-fis1-links-to-cell-cycle-regulators-at-g2-m-transition
#20
Seungmin Lee, Yong-Yea Park, Song-Hee Kim, Oanh T Kim Nguyen, Young-Suk Yoo, Gordon K Chan, Xuejun Sun, Hyeseong Cho
We have previously shown that prolonged mitochondrial elongation triggers cellular senescence. Here, we report that enforced mitochondrial elongation by hFis1 depletion caused a severe defect in cell cycle progression through G2/M phase (~3-fold reduction in mitotic index; p < 0.01). Reintroduction of Myc-hFis1 to these cells induced mitochondrial fragmentation and restored the cell cycle, indicating that morphodynamic changes of mitochondria closely link to the cell cycle. In hFis1-knockdown cells, cell cycle regulators governing the G2/M phase, including cyclin A, cyclin B1, cyclin-dependent kinase1 (Cdk1), polo-like kinase1 (Plk1), aurora kinase A and Mad2, were significantly suppressed (2- to 10-fold)...
February 2014: Cellular and Molecular Life Sciences: CMLS
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