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FoxM1 AND MYC

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https://www.readbyqxmd.com/read/29786110/multi%C3%A2-layered-prevention-and-treatment-of-chronic-inflammation-organ-fibrosis-and-cancer-associated-with-canonical-wnt-%C3%AE-%C3%A2-catenin-signaling-activation-review
#1
Masaru Katoh
β‑catenin/CTNNB1 is an intracellular scaffold protein that interacts with adhesion molecules (E‑cadherin/CDH1, N‑cadherin/CDH2, VE‑cadherin/CDH5 and α‑catenins), transmembrane‑type mucins (MUC1/CD227 and MUC16/CA125), signaling regulators (APC, AXIN1, AXIN2 and NHERF1/EBP50) and epigenetic or transcriptional regulators (BCL9, BCL9L, CREBBP/CBP, EP300/p300, FOXM1, MED12, SMARCA4/BRG1 and TCF/LEF). Gain‑of‑function CTTNB1 mutations are detected in bladder cancer, colorectal cancer, gastric cancer, liver cancer, lung cancer, pancreatic cancer, prostate cancer and uterine cancer, whereas loss‑of‑function CTNNB1 mutations are also detected in human cancer...
August 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29554906/transcription-factor-foxm1-is-the-downstream-target-of-c-myc-and-contributes-to-the-development-of-prostate-cancer
#2
Huafeng Pan, Yudi Zhu, Wei Wei, Siliang Shao, Xin Rui
BACKGROUND: Prostate cancer is a common malignancy and the second leading cause of cancer death in men. Elevated expression of the transcription factor FoxM1 and c-Myc has been identified in prostate cancer. However, the potential mechanism of elevated FoxM1 and c-Myc to the development of prostate cancer has not been identified. METHODS: In this report, the mRNA level of FoxM1 and c-Myc was detected in 30 prostate cancer and para-cancer tissues. Then, we detected the expression level of FoxM1 by real-time PCR and Western blot after disturbance of the expression level of c-Myc in PC-3 cells...
March 20, 2018: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29472532/co-inhibition-of-bet-proteins-and-nf-%C3%AE%C2%BAb-as-a-potential-therapy-for-colorectal-cancer-through-synergistic-inhibiting-myc-and-foxm1-expressions
#3
Tingyu Wu, Guanghui Wang, Wei Chen, Zhehui Zhu, Yun Liu, Zhenyu Huang, Yuji Huang, Peng Du, Yili Yang, Chen-Ying Liu, Long Cui
The bromodomain and extra-terminal domain inhibitors (BETi) are promising epigenetic drugs for the treatment of various cancers through suppression of oncogenic transcription factors. However, only a subset of colorectal cancer (CRC) cells response to BETi. We investigate additional agents that could be combined with BETi to overcome this obstacle. JQ1-resistant CRC cells were used for screening of the effective combination therapies with JQ1. RNA-seq was performed to explore the mechanism of synergistic effect...
February 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29306020/a-selective-cyclin-dependent-kinase-4-6-dual-inhibitor-ribociclib-lee011-inhibits-cell-proliferation-and-induces-apoptosis-in-aggressive-thyroid-cancer
#4
Hyun Joo Lee, Woo Kyung Lee, Chan Woo Kang, Cheol Ryong Ku, Yoon Hee Cho, Eun Jig Lee
The RB-E2F1 pathway is an important mechanism of cell-cycle control, and deregulation of this pathway is one of the key factors contributing to tumorigenesis. Cyclin-dependent kinases (CDKs) and Cyclin D have been known to increase in aggressive thyroid cancer. However, there has been no study to investigate effects of a selective CDK 4/6 inhibitor, Ribociclib (LEE011), in thyroid cancer. Performing Western blotting, we found that RB phosphorylation and the expression of Cyclin D are significantly higher in papillary thyroid cancer (PTC) cell lines as well as anaplastic thyroid cancer (ATC) cell lines, compared with normal thyroid cell line and follicular thyroid cancer cell line...
March 28, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29303511/a-gene-expression-signature-of-foxm1-predicts-the-prognosis-of-hepatocellular-carcinoma
#5
Bic-Na Song, In-Sun Chu
FOXM1 (Forkhead box M1) is a key regulator of tumorigenesis. Previous studies demonstrated that FOXM1 overexpression was strongly correlated with poor prognosis in various cancers, including hepatocellular carcinoma (HCC). In this study, we examined an association between the gene expression signature of FOXM1 and HCC patient outcome. The co-expressed gene set of FOXM1, which is significantly associated with the prognosis of HCC patients, was identified by analyzing the gene expression profiles of 100 patients with HCC, and this gene set was validated in two independent HCC patient cohorts (n=573)...
January 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29175329/inhibition-of-cip2a-attenuates-tumor-progression-by-inducing-cell-cycle-arrest-and-promoting-cellular-senescence-in-hepatocellular-carcinoma
#6
Xue Yang, Kai Qu, Jie Tao, Guozhi Yin, Shaoshan Han, Qingguang Liu, Hao Sun
CIP2A is a recent identified oncogene that inhibits protein phosphatase 2A (PP2A) and stabilizes c-Myc in cancer cells. To investigate the potential oncogenic role and prognostic value of CIP2A, we comprehensively analyzed the CIP2A expression levels in pan-cancer and observed high expression level of CIP2A in majority cancer types, including hepatocellular carcinoma (HCC). Based on a validation cohort including 60 HCC and 20 non-tumorous tissue samples, we further confirmed the high mRNA and protein expression levels of CIP2A in HCC, and found high CIP2A mRNA expression level was associated with unfavorable overall and recurrence-free survival in patients with HCC...
January 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29138846/itr%C3%A2-284-modulates-cell-differentiation-in-human-chronic-myelogenous-leukemia-k562-cells
#7
Jai-Sing Yang, Chao-Ying Lee, Hsin-Chung Cho, Chi-Cheng Lu, Sheng-Chu Kuo, Yen-Fang Wen, Fuu-Jen Tsai, Miau-Rong Lee, Shih-Chang Tsai
ITR‑284 is a carboxamide analog that can inhibit proliferation in human promyelocytic leukemia HL-60 cells. To understand the effects and molecular mechanisms of ITR‑284 in human erythromyeloblastoid leukemia, we treated K562 cells with different concentrations of ITR‑284 (0, 2, 4, 6, 8 and 10 nM) and all-trans retinoic acid (ATRA) (0, 0.1, 0.5, 1, 5 and 10 µM) for 24 h. The IC50 of ITR‑284 was ~10 nM in K562 cells treated for 24 h as determined by MTT assay. May-Grünwald-Giemsa staining and nitro blue tetrazolium (NBT) assays were used to determine cell morphology changes and differentiation after ITR‑284 and ATRA treatment...
January 2018: Oncology Reports
https://www.readbyqxmd.com/read/28978307/mir-216b-inhibits-cell-proliferation-by-targeting-foxm1-in-cervical-cancer-cells-and-is-associated-with-better-prognosis
#8
Shanyang He, Bing Liao, Yalan Deng, Chang Su, Jiuling Tuo, Jun Liu, Shuzhong Yao, Lin Xu
BACKGROUND: Our previous study showed FOXM1 expression was significantly up-regulated in cervical cancer, and was associated with poor prognosis. To clarify miRNAs-FOXM1 modulation pathways, in this study, we investigated the relationships between miR-216b and FOXM1 and the role of miR-216b in cell proliferation and prognosis of cervical cancer patients. METHODS: Western blotting and qPCR were used to determine expression of FOXM1, cell cycle related factors and miR-216b level...
October 4, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28903501/sex-differential-responses-of-tumor-promotion-associated-genes-and-dysregulation-of-novel-long-noncoding-rnas-in-constitutive-androstane-receptor-activated-mouse-liver
#9
Nicholas J Lodato, Tisha Melia, Andy Rampersaud, David J Waxman
Xenobiotic agonists of constitutive androstane receptor (CAR) induce many hepatic drug metabolizing enzymes, but following prolonged exposure, promote hepatocellular carcinoma, most notably in male mouse liver. Here, we used nuclear RNA-seq to characterize global changes in the mouse liver transcriptome following exposure to the CAR-specific agonist ligand 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), including changes in novel long noncoding RNAs that may contribute to xenobiotic-induced pathophysiology...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28806394/smggds-is-a-transient-nucleolar-protein-that-protects-cells-from-nucleolar-stress-and-promotes-the-cell-cycle-by-regulating-dream-complex-gene-expression
#10
P Gonyo, C Bergom, A C Brandt, S-W Tsaih, Y Sun, T M Bigley, E L Lorimer, S S Terhune, H Rui, M J Flister, R M Long, C L Williams
The chaperone protein and guanine nucleotide exchange factor SmgGDS (RAP1GDS1) is a key promoter of cancer cell proliferation and tumorigenesis. SmgGDS undergoes nucleocytoplasmic shuttling, suggesting that it has both cytoplasmic and nuclear functions that promote cancer. Previous studies indicate that SmgGDS binds cytoplasmic small GTPases and promotes their trafficking to the plasma membrane. In contrast, little is known about the functions of SmgGDS in the nucleus, or how these nuclear functions might benefit cancer cells...
December 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28539830/dna-methylation-mediated-down-regulation-of-mir-370-regulates-cell-growth-through-activation-of-the-wnt-%C3%AE-catenin-signaling-pathway-in-human-osteosarcoma-cells
#11
Wentao Zhang, Ning Duan, Qian Zhang, Tao Song, Zhong Li, Caiguo Zhang, Xun Chen, Kunzheng Wang
MicroRNA-370 (miR-370) has been observed to act as a tumor suppressor through the targeting of different proteins in a variety of tumors. Our previous study indicated that miR-370 was able to target forkhead box protein M1 (FOXM1) to inhibit cell growth and metastasis in human osteosarcoma cells. In this study, we reported that FOXM1 interacted with β-catenin in vitro and in vivo . Similar to FOXM1, critical components of the Wnt signaling pathway, including β-catenin, c-Myc, and Cyclin D1, were also highly expressed in different human osteosarcoma cells lines...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28416635/vprbp-dcaf1-regulates-the-degradation-and-nonproteolytic-activation-of-the-cell-cycle-transcription-factor-foxm1
#12
Xianxi Wang, Anthony Arceci, Kelly Bird, Christine A Mills, Rajarshi Choudhury, Jennifer L Kernan, Chunxiao Zhou, Victoria Bae-Jump, Albert Bowers, Michael J Emanuele
The oncogenic transcription factor FoxM1 plays a vital role in cell cycle progression, is activated in numerous human malignancies, and is linked to chromosome instability. We characterize here a cullin 4-based E3 ubiquitin ligase and its substrate receptor, VprBP/DCAF1 (CRL4VprBP ), which we show regulate FoxM1 ubiquitylation and degradation. Paradoxically, we also found that the substrate receptor VprBP is a potent FoxM1 activator. VprBP depletion reduces expression of FoxM1 target genes and impairs mitotic entry, whereas ectopic VprBP expression strongly activates a FoxM1 transcriptional reporter...
July 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28281307/integrated-expression-analysis-identifies-transcription-networks-in-mouse-and-human-gastric-neoplasia
#13
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 (GC) 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 < ...
July 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28114286/foxm1-recruits-nuclear-aurora-kinase-a-to-participate-in-a-positive-feedback-loop-essential-for-the-self-renewal-of-breast-cancer-stem-cells
#14
N Yang, C Wang, Z Wang, S Zona, S-X Lin, X Wang, M Yan, F-M Zheng, S-S Li, B Xu, L Bella, J-S Yong, E W-F Lam, Q Liu
Substantial evidence suggests that breast cancer initiation, recurrence and drug resistance is supported by breast cancer stem cells (BCSCs). Recently, we reported a novel role of Aurora kinase A (AURKA) in BCSCs, as a transactivating co-factor in the induction of the c-Myc oncoprotein. However, the mode of action and transcriptional network of nuclear AURKA in BCSCs remain unknown. Here, we report that nuclear AURKA can be recruited by Forkhead box subclass M1 (FOXM1) as a co-factor to transactivate FOXM1 target genes in a kinase-independent manner...
June 15, 2017: Oncogene
https://www.readbyqxmd.com/read/27612430/restoring-mir122-in-human-stem-like-hepatocarcinoma-cells-prompts-tumor-dormancy-through-smad-independent-tgf-%C3%AE-pathway
#15
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...
November 1, 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
#16
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...
February 16, 2017: Oncogene
https://www.readbyqxmd.com/read/27451973/a-novel-slug-containing-negative-feedback-loop-regulates-scf-c-kit-mediated-hematopoietic-stem-cell-self-renewal
#17
Z Zhang, P Zhu, Y Zhou, Y Sheng, Y Hong, D Xiang, Z Qian, J Mosenson, W-S Wu
The stem cell factor (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...
February 2017: 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
#18
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
#19
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
#20
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
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