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https://www.readbyqxmd.com/read/28819152/dissecting-the-genomic-activity-of-a-transcriptional-regulator-by-the-integrative-analysis-of-omics-data
#1
Giulio Ferrero, Valentina Miano, Marco Beccuti, Gianfranco Balbo, Michele De Bortoli, Francesca Cordero
In the study of genomic regulation, strategies to integrate the data produced by Next Generation Sequencing (NGS)-based technologies in a meaningful ensemble are eagerly awaited and must continuously evolve. Here, we describe an integrative strategy for the analysis of data generated by chromatin immunoprecipitation followed by NGS which combines algorithms for data overlap, normalization and epigenetic state analysis. The performance of our strategy is illustrated by presenting the analysis of data relative to the transcriptional regulator Estrogen Receptor alpha (ERα) in MCF-7 breast cancer cells and of Glucocorticoid Receptor (GR) in A549 lung cancer cells...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808999/studying-protein-protein-interactions-by-biotin-ap-tagged-pulldown-and-ltq-orbitrap-mass-spectrometry
#2
Zhongqiu Xie, Yuemeng Jia, Hui Li
The study of protein-protein interactions represents a key aspect of biological research. Identifying unknown protein binding partners using mass spectrometry (MS)-based proteomics has evolved into an indispensable strategy in drug discovery. The classic approach of immunoprecipitation with specific antibodies against the proteins of interest has limitations, such as the need for immunoprecipitation-qualified antibody. The biotin AP-tag pull-down system has the advantage of high specificity, ease of use, and no requirement for antibody...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28807830/usp5-promotes-tumorigenesis-and-progression-of-pancreatic-cancer-by-stabilizing-foxm1-protein
#3
Xin-Yan Li, Hai-Yun Wu, Xiao-Fang Mao, Li-Xin Jiang, Yong-Xiang Wang
Increased ubiquitin-specific protease 5 (USP5) has been associated with tumorigenesis of malignancy including glioblastoma, melanoma and hepatocellular carcinoma. However, the role of USP5 in tumorigenesis of pancreatic ductal adenocarcinoma (PDAC) has not been studied yet. In this study, we demonstrated that USP5 was significantly upregulated in a panel of PDAC cell lines and correlated with FoxM1 protein expression. USP5 knockdown inhibited proliferation of PANC-1 and SW1990, two PDAC cell lines. In the mouse xenografted pancreatic tumor model, suppression of USP5 significantly decreased tumor growth, correlated with down regulation of FoxM1...
August 11, 2017: Biochemical and Biophysical Research Communications
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
#4
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...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28802012/the-inhibitory-effect-of-5-7-dmf-on-pancreatic-sphere-forming-cell-function-mediated-by-foxm1-gene-expression
#5
Deyu Zeng, Jian Ma, Rongrong Li, Jianfeng Yang, Xianli Yin
Pancreatic cancer is one of the major human malignant tumors severely endangering human health and life with high mortality due to the concealment of early symptoms and lack of effective therapies during advanced stages. The identification of pancreatic cancer stem cell functions has been as important strategy for understanding of pancreatic cancer biology and novel drug and therapy development. In the present study, we successfully isolated the pancreatic sphere-forming cells from pancreatic cancer cell line PANC-1 by sphere-forming method and we found that the sphere-forming ability and the cell migration rate of pancreatic sphere-forming cells were significantly inhibited by 5,7-DMF treatment, which was supported by the corresponding changes of several EMT biomarkers after being treated with 5,7-DMF...
August 12, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28799433/cell-cycle-transcription-control-dream-muvb-and-rb-e2f-complexes
#6
Martin Fischer, Gerd A Müller
The precise timing of cell cycle gene expression is critical for the control of cell proliferation; de-regulation of this timing promotes the formation of cancer and leads to defects during differentiation and development. Entry into and progression through S phase requires expression of genes coding for proteins that function in DNA replication. Expression of a distinct set of genes is essential to pass through mitosis and cytokinesis. Expression of these groups of cell cycle-dependent genes is regulated by the RB pocket protein family, the E2F transcription factor family, and MuvB complexes together with B-MYB and FOXM1...
August 11, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28782484/gene-expression-meta-analysis-of-potential-metastatic-breast-cancer-markers
#7
R Bell, R Barraclough, O Vasieva
Breast cancer metastasis is a highly prevalent cause of death for European females. DNA microarray analysis has established that primary tumors, which remain localized, differ in gene expression from those that metastasize. The aim of the project was to validate suggested prognostic and therapeutic markers using meta-analysis of data on gene expression in metastatic and primary breast cancer tumors combined from 12 studies available from the Genevestigator database. Our analysis suggested that transcriptional expression of the COX2 gene is significantly downregulated in metastatic tissue compared to normal breast tissue, but is not downregulated in primary tumors compared with normal breast tissue and may be used as a differential marker in metastatic breast cancer diagnostics...
August 7, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28777741/critical-roles-of-smyd2-mediated-%C3%AE-catenin-methylation-for-nuclear-translocation-and-activation-of-wnt-signaling
#8
Xiaolan Deng, Ryuji Hamamoto, Theodore Vougiouklakis, Rui Wang, Yuichiro Yoshioka, Takehiro Suzuki, Naoshi Dohmae, Yo Matsuo, Jae-Hyun Park, Yusuke Nakamura
Accumulation of β-catenin in the nucleus is a hallmark of activation of the Wnt/β-catenin signaling pathway, which drives development of a large proportion of human cancers. However, the mechanism of β-catenin nuclear translocation has not been well investigated. Here we report biological significance of SMYD2-mediated lysine 133 (K133) methylation of β-catenin on its nuclear translocation. Knockdown of SMYD2 attenuates the------ nuclear localization of β-catenin protein in human cancer cells. Consequently, transcriptional levels of well-known Wnt-signaling molecules, cMYC and CCND1, are significantly reduced...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28770020/oxidative-stress-gene-expression-profile-correlates-with-cancer-patient-poor-prognosis-identification-of-crucial-pathways-might-select-novel-therapeutic-approaches
#9
REVIEW
Alessandra Leone, Maria Serena Roca, Chiara Ciardiello, Susan Costantini, Alfredo Budillon
The role of altered redox status and high reactive oxygen species (ROS) is still controversial in cancer development and progression. Intracellular levels of ROS are elevated in cancer cells suggesting a role in cancer initiation and progression; on the contrary, ROS elevated levels may induce programmed cell death and have been associated with cancer suppression. Thus, it is crucial to consider the double-face of ROS, for novel therapeutic strategies targeting redox regulatory mechanisms. In this review, in order to derive cancer-type specific oxidative stress genes' profile and their potential prognostic role, we integrated a publicly available oxidative stress gene signature with patient survival data from the Cancer Genome Atlas database...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28767320/forkhead-box-m1-positively-regulates-ube2c-and-protects-glioma-cells-from-autophagic-death
#10
Liang Guo, Zhiming Ding, Nunu Huang, Zhengsong Huang, Nu Zhang, Zhibo Xia
Ubiquitin-conjugating enzyme E2C (UBE2C) is characterized as a crucial molecule in cancer cell growth that plays an essential role in the development of gliomas, but the detailed mechanisms have not been fully elucidated. In this study, we found that Forkhead box transcription factor M1 (FoxM1) overexpression increased UBE2C expression, whereas FoxM1 suppression inhibited UBE2C expression in glioma cells. In addition, high FoxM1/UBE2C expression was significantly correlated with poor prognosis in glioma. We subsequently demonstrated that UBE2C was a direct transcriptional target of FoxM1, and site-directed mutations markedly down-regulated UBE2C promoter activity...
August 2, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28759137/soft-tissue-sarcomas-from-a-morphological-to-a-molecular-biological-approach
#11
REVIEW
Yoshinao Oda, Hidetaka Yamamoto, Kenichi Kohashi, Yuichi Yamada, Kunio Iura, Takeaki Ishii, Akira Maekawa, Hirofumi Bekki
Recently developed molecular genetic techniques have led to the elucidation of tumor-specific genomic alterations and thereby the reclassification of tumor entities of soft tissue sarcoma. A solitary fibrous tumor-mimicking tumor with the AHRR-NCOA2 gene has been isolated as angiofibroma of soft tissue. As for small round cell sarcomas, novel fusion genes such as CIC-DUX4 and BCOR-CCNB3 have been identified in these tumor groups. SMARCB1/INI1 deficient tumors with round cell morphology are also expected to be reclassified in three types, based on the combination of their morphology and genotype...
July 31, 2017: Pathology International
https://www.readbyqxmd.com/read/28754864/foxm1-facilitates-gastric-cancer-cell-migration-and-invasion-by-inducing-cathepsin-d
#12
Li Yang, Ming Cui, Liang Zhang, Lei Song
Forkhead box M1 (FOXM1) has been reported as a vital transcription factor in different human malignancies. To date, the mechanisms of FOXM1 in modulating the invasion and metastasis of gastric cancer cells have not been elucidated. In the present study, we found that overexpression of FOXM1 prompted cell migration and invasion of gastric cancer, and increased the expression of Cathepsin D (Cath-D). However, FOXM1 siRNA repressed cell migration and invasion, and also decreased the expression of Cath-D in gastric cancer cells...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28743512/inferring-transcription-factor-activity-from-microarray-data-reveals-novel-targets-for-toxicological-investigations
#13
T M Souza, T van den Beucken, J C S Kleinjans, D G J Jennen
Transcription factors (TFs) are important modulators of the inducible portion of the transcriptome, and therefore relevant in the context of exposure to exogenous compounds. Current approaches to predict the activity of TFs in biological systems are usually restricted to a few entities at a time due to low-throughput techniques targeting a limited fraction of annotated human TFs. Therefore, high-throughput alternatives may help to identify new targets of mechanistic and predictive value in toxicological investigations...
July 22, 2017: Toxicology
https://www.readbyqxmd.com/read/28731180/mir-216b-inhibits-glioma-cell-migration-and-invasion-through-suppression-of-foxm1
#14
Tingting Zhang, Guangtao Ma, Yan Zhang, Hongda Huo, Yuqian Zhao
MicroRNAs (miRNAs) play a vital role in tumour biological and pathologic processes. In the present study, we aimed to detect the expression and biological role of miR-216b in glioma. Our data showed that miR-216b was significantly downregulated in human glioma tissues and cells. Ectopic expression of miR-216b inhibited the proliferation and invasion of U87 and U251 cells and suppressed the growth of xenograft tumours in vivo. Bioinformatic and luciferase reporter analyses identified Forkhead box protein M1 (FoxM1) as a direct target of miR-216b...
July 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28705772/improving-pharmacological-targeting-of-akt-in-melanoma
#15
Omer F Kuzu, Raghavendra Gowda, Arati Sharma, Mohammad A Noory, Saketh S Dinavahi, Gregory Kardos, Joseph J Drabick, Gavin P Robertson
Targeting AKT with pharmacological agents inhibiting this protein in the melanoma clinic is ineffective. This is a major contradiction considering the substantial preclinical data suggesting AKT as an effective target. Various approaches have been undertaken to unravel this contradiction and drug combinations sought that could resolve this concern. We have shown that genetic targeting AKT3 or WEE1 can be effective for inhibiting tumor growth in preclinical animal models. However, no one has examined whether combining pharmacological agents targeting each of these enzymes could be more effective than inhibiting each alone and enhance the efficacy of targeting AKT in melanoma...
July 11, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28701892/a-pilot-study-of-post-operative-adjuvant-vaccine-for-advanced-gastric-cancer
#16
Yoshiyuki Fujiwara, Keijiro Sugimura, Hiroshi Miyata, Takeshi Omori, Hiroyuki Nakano, Chie Mochizuki, Katsuji Shimizu, Hiroaki Saito, Keigo Ashida, Soichiro Honjyo, Yusuke Nakamura, Masahiko Yano
BACKGROUND: Previously, we had performed a clinical study using human leukocyte antigen (HLA)-A24-binding peptide vaccines containing a combination of novel cancer-testis antigens and anti-angiogenic peptides derived from DEPDC1, URLC10, FOXM1, KIF20A and VEGFR1 for advanced gastric cancer (AGC) patients who were refractory to chemotherapy. We applied the cocktail vaccine to the combination therapy with S-1 for patients with AGC as a post-operative adjuvant therapy and performed this clinical pilot study...
June 2017: Yonago Acta Medica
https://www.readbyqxmd.com/read/28692634/targeting-foxm1-improves-cytotoxicity-of-paclitaxel-and-cisplatinum-in-platinum-resistant-ovarian-cancer
#17
Gina L Westhoff, Yi Chen, Nelson N H Teng
OBJECTIVE: Aberrantly activated FOXM1 (forkhead box protein M1) leading to uncontrolled cell proliferation and dysregulation of FOXM1 transcription network occurs in 84% of ovarian cancer cases. It was demonstrated that thiostrepton, a thiazole antibiotic, decreases FOXM1 expression. We aimed to determine if targeting the FOXM1 pathway with thiostrepton could improve the efficacy of paclitaxel and cisplatin in human ovarian cancer ascites cells ex vivo. METHODS: Human ovarian cancer cell lines and patients' ascites cells were treated with paclitaxel, cisplatin, and thiostrepton or a combination for 48 hours, and cytotoxicity was assessed...
July 7, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28685059/downregulating-forkhead-box-m1-inhibits-proliferation-by-inhibiting-autophagy-in-the-sw480-cell-line
#18
Shibiao Zhong, Aiyan Zhou, Fanghua Qi, Zhen Li, Zeyan Yu, Yongchao Lu, Xudong Liu
Forkhead Box M1 (FoxM1) is one of the most important oncogenes, and overexpression of FoxM1 has been reported in many cancers, including colon cancer. In the present study, the authors attempted to reveal the mechanism underlying its effects on proliferation through autophagy in the sw480 cell line. FoxM1 is knocked down through short hairpin (sh)RNA in the sw480 cell line. A series of experiments were conducted to examine it function on proliferation and LC3 and P62 were used to measure level of autophagy...
July 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28677763/tetramethylpyrazine-inhibits-prostate-cancer-progression-by-downregulation-of-forkhead-box-m1
#19
Yi Zhou, Zhigang Ji, Weigang Yan, Zhien Zhou, Hanzhong Li, Yu Xiao
Tetramethylpyrazine (TMP) has exhibited various anticancer effects. However, its ability to inhibit proliferation, migration, and invasion of prostate cancer (PCa) PC-3 cells is still unclear. In the present study, different concentrations of TMP were co-incubated with PC-3 cells. The pcDNA-FOXM1 plasmid was transfected into cells before treatment with 500 µg/l TMP. The proliferative, migratory and invasive abilities of PC-3 cells were tested by MTT assay, wound healing assay and colony formation assay. Western blotting was used to investigate the expression of FOXM1...
June 29, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28666461/glyceollins-trigger-anti-proliferative-effects-through-estradiol-dependent-and-independent-pathways-in-breast-cancer-cells
#20
Sylvain Lecomte, Frederic Chalmel, François Ferriere, Frederic Percevault, Nicolas Plu, Christian Saligaut, Claire Surel, Marie Lelong, Theo Efstathiou, Farzad Pakdel
BACKGROUND: Estrogen receptors (ER) α and β are found in both women and men in many tissues, where they have different functions, including having roles in cell proliferation and differentiation of the reproductive tract. In addition to estradiol (E2), a natural hormone, numerous compounds are able to bind ERs and modulate their activities. Among these compounds, phytoestrogens such as isoflavones, which are found in plants, are promising therapeutics for several pathologies. Glyceollins are second metabolites of isoflavones that are mainly produced in soybean in response to an elicitor...
June 30, 2017: Cell Communication and Signaling: CCS
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