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Sheng Li, Chengzhong Wang, Weikai Wang, Weidong Liu, Guiqin Zhang
This study aimed to explore the underlying mechanism of relapsed acute lymphoblastic leukemia (ALL).Datasets of GSE28460 and GSE18497 were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between diagnostic and relapsed ALL samples were identified using Limma package in R, and a Venn diagram was drawn. Next, functional enrichment analyses of co-regulated DEGs were performed. Based on the String database, protein-protein interaction network and module analyses were also conducted...
May 2018: Medicine (Baltimore)
Liang Xu, Ye Chen, Anand Mayakonda, Lynnette Koh, Yuk Kien Chong, Dennis L Buckley, Edwin Sandanaraj, See Wee Lim, Ruby Yu-Tong Lin, Xin-Yu Ke, Mo-Li Huang, Jianxiang Chen, Wendi Sun, Ling-Zhi Wang, Boon Cher Goh, Huy Q Dinh, Dennis Kappei, Georg E Winter, Ling-Wen Ding, Beng Ti Ang, Benjamin P Berman, James E Bradner, Carol Tang, H Phillip Koeffler
Competitive BET bromodomain inhibitors (BBIs) targeting BET proteins (BRD2, BRD3, BRD4, and BRDT) show promising preclinical activities against brain cancers. However, the BET protein-dependent glioblastoma (GBM)-promoting transcriptional network remains elusive. Here, with mechanistic exploration of a next-generation chemical degrader of BET proteins (dBET6), we reveal a profound and consistent impact of BET proteins on E2F1- dependent transcriptional program in both differentiated GBM cells and brain tumor-initiating cells...
May 15, 2018: Proceedings of the National Academy of Sciences of the United States of America
Chai-Jin Lee, Dongwon Kang, Sangseon Lee, Sunwon Lee, Jaewoo Kang, Sun Kim
Determining functions of a gene requires time consuming, expensive biological experiments. Scientists can speed up this experimental process if the literature information and biological networks can be adequately provided. In this paper, we present a web-based information system that can perform in silico experiments of computationally testing hypothesis on the function of a gene. A hypothesis that is specified in English by the user is converted to genes using a literature and knowledge mining system called BEST...
May 11, 2018: Methods: a Companion to Methods in Enzymology
Melina M Musri, Núria Coll-Bonfill, Bradley A Maron, Víctor I Peinado, Ruisheng Wang, Jordi Altirriba, Isabel Blanco, William M Oldham, Olga Tura-Ceide, Jessica García-Lucio, Benjamin de la Cruz-Thea, Gunter Meister, Joseph Loscalzo, Joan A Barberà
BACKGROUND: Pulmonary vascular remodeling is an angiogenic-related process involving changes in smooth muscle cell (SMC) homeostasis, which is frequently observed in chronic obstructive pulmonary disease (COPD). MicroRNAs (miRNAs) are small non-coding RNAs that regulate mRNA expression levels of many genes leading to the manifestation of cell identity and specific cellular phenotypes. Here we evaluate the miRNA expression profiles of pulmonary arteries (PA) of patients with COPD and its relationship with the regulation of SMC phenotypic change...
May 14, 2018: American Journal of Respiratory Cell and Molecular Biology
Cheng-Cao Sun, Qun Zhou, Wei Hu, Shu-Jun Li, Feng Zhang, Zhen-Long Chen, Guang Li, Zhuo-Yue Bi, Yong-Yi Bi, Feng-Yun Gong, Tao Bo, Zhan-Peng Yuan, Wei-Dong Hu, Bo-Tao Zhan, Qian Zhang, Qi-Zhu Tang, De-Jia Li
E2F is a group of genes that encode a family of transcription factors (TFs) in higher eukaryotes and participate in cell cycle regulation and DNA synthesis in mammalian cells. Evidence from cell lines, mouse models, and human tissues indicates that TFs are implicated in lung cancer (LC) tumorigenesis. However, the diverse expression patterns and prognostic values of eight E2Fs have yet to be elucidated. In the current study, we examined the transcriptional and survival data of E2Fs in patients with LC from ONCOMINE, GEPIA, Kaplan-Meier Plotter, and cBioPortal databases...
May 11, 2018: Aging
Garam Kim, Jin-Young Kim, Sung-Chul Lim, Kwang Youl Lee, Okyun Kim, Hong Seok Choi
Melanoma is among the most aggressive and treatment-resistant human cancers. Aberrant histone H3 methylation at Lys 9 (H3K9) correlates with carcinogenic gene silencing, but the significance of suppressor of variegation 3-9 homolog 1 (SUV39H1), an H3K9-specific methyltransferase, in melanoma initiation and progression remains unclear. Here, we show that SUV39H1-mediated H3K9 trimethylation facilitates retinoblastoma ( RB) 1 promoter CpG island methylation by interacting with DNA methyltransferase 3A and decreasing RB mRNA and protein in melanoma cells...
May 11, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Florian Rouaud, Nedra Hamouda-Tekaya, Michaël Cerezo, Patricia Abbe, Joséphine Zangari, Veronique Hofman, Mickaël Ohanna, Baharia Mograbi, Najla El-Hachem, Zohra Benfodda, Alexandre Lebeau, Meri K Tulic, Paul Hofman, Corine Bertolotto, Thierry Passeron, Jean-Sébastien Annicotte, Robert Ballotti, Stéphane Rocchi
Melanoma is one of the most lethal cancers when it reaches a metastatic stage. Despite advancements in targeted therapies (BRAF inhibitors) or immunotherapies (anti-CTLA-4 or anti-PD1), most patients with melanoma will need additional treatment. Thus, there is an urgent need to develop new therapeutical approaches to bypass resistance and achieve more prolonged responses. In this context, we were interested in E2F1, a transcription factor that plays a major role in the control of cell cycle under physiological and pathological conditions...
May 9, 2018: Cell Death & Disease
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No abstract text is available yet for this article.
March 1, 2018: Cancer Research
Shufang Jin, Hailong Ma, Wenyi Yang, Houyu Ju, Lizhen Wang, Zhiyuan Zhang
Cell division cycle 7 (Cdc7) plays important roles in the regulation of the initiation of DNA replication throughout S phase. Whether inhibition of Cdc7 has a direct antitumour effect in oral squamous cell carcinoma (OSCC) remains unclear. In this study, XL413, a novel Cdc7 inhibitor, markedly inhibited the viability of OSCC cells but not that of non-tumour primary cells. There was a synergistic effect between XL413 and DNA-damaging agents (e.g. cisplatin and 5-fluorouracil) on OSCC in vitro and in vivo. Moreover, XL413 exhibited a notable antitumour effect on OSCC patients with high Cdc7 expression in mini patient-derived xenografts model...
April 30, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Jiřina Procházková, Simona Strapáčová, Lucie Svržková, Zdeněk Andrysík, Martina Hýžďalová, Eva Hrubá, Kateřina Pěnčíková, Helena Líbalová, Jan Topinka, Jiří Kléma, Joaquín M Espinosa, Jan Vondráček, Miroslav Machala
Exposure to persistent ligands of aryl hydrocarbon receptor (AhR) has been found to cause lung cancer in experimental animals, and lung adenocarcinomas are often associated with enhanced AhR expression and aberrant AhR activation. In order to better understand the action of toxic AhR ligands in lung epithelial cells, we performed global gene expression profiling and analyze TCDD-induced changes in A549 transcriptome, both sensitive and non-sensitive to CH223191 co-treatment. Comparison of our data with results from previously reported microarray and ChIP-seq experiments enabled us to identify candidate genes, which expression status reflects exposure of lung cancer cells to TCDD, and to predict processes, pathways (e...
April 25, 2018: Toxicology Letters
Wooyoung Jeong, Seoungo Jung, Fuller W Bazer, Jinyoung Kim
In the uterine environment, the pre-implantation embryo adapts to low oxygen concentrations through intracellular responses including modification of gene expression, progression via the cell cycle and metabolism. In this study, we determined mechanisms underlying the adaptation of pig embryos to oxygen deficiency in the maternal-conceptus microenvironment in in vitro experiments using our established porcine trophectoderm (pTr) cells in culture. The transition from G1 to S phase in pTr cells was reduced in response to 2% oxygen during a short period (<24 h), and the hypoxia-induced G1 arrest was reversible during prolonged hypoxia exposure...
April 14, 2018: Theriogenology
Sana AlQarni, Yazeed Al-Sheikh, Donald Campbell, Mark Drotar, Adele Hannigan, Shelagh Boyle, Pawel Herzyk, Andrew Kossenkov, Kate Armfield, Lauren Jamieson, Mariarca Bailo, Paul M Lieberman, Penelope Tsimbouri, Joanna B Wilson
Epstein-Barr virus (EBV)-associated Burkitt's lymphoma is characterised by the deregulation of c-Myc expression and a restricted viral gene expression pattern in which the EBV nuclear antigen-1 (EBNA1) is the only viral protein to be consistently expressed. EBNA1 is required for viral genome propagation and segregation during latency. However, it has been much debated whether the protein plays a role in viral-associated tumourigenesis. We show that the lymphomas which arise in EµEBNA1 transgenic mice are unequivocally linked to EBNA1 expression and that both C-Myc and Mdm2 deregulation are central to this process...
April 25, 2018: Oncogene
Feng Leng, Jiekai Yu, Chunxiao Zhang, Salvador Alejo, Nam Hoang, Hong Sun, Fei Lu, Hui Zhang
Many non-histone proteins are lysine methylated and a novel function of this modification is to trigger the proteolysis of methylated proteins. Here, we report that the methylated lysine 142 of DNMT1, a major DNA methyltransferase that preserves epigenetic inheritance of DNA methylation patterns during DNA replication, is demethylated by LSD1. A novel methyl-binding protein, L3MBTL3, binds the K142-methylated DNMT1 and recruits a novel CRL4DCAF5 ubiquitin ligase to degrade DNMT1. Both LSD1 and PHF20L1 act primarily in S phase to prevent DNMT1 degradation by L3MBTL3-CRL4DCAF5 ...
April 24, 2018: Nature Communications
Sanjay Singh, Manish Gupta, Rajeev Kumar Seam, Harish Changotra
INTRODUCTION: Altered expression of many E2F family members have been reported in various human cancers. In this study, we investigated the role of non-synonymous single nucleotide polymorphisms (rs3213172 C/T, rs3213173 C/T, and rs3213176 G/A) of the gene E2F1 with cervical cancer. METHODS: A total of 181 samples including 90 cervical cancer patients and 91 healthy controls were genotyped. The genotype frequencies of these polymorphisms in collected samples were determined by either PCR-RFLP or PCR-ARFLP methods...
April 1, 2018: International Journal of Biological Markers
Z Zhang, S-Y Li, L-B Zhang
OBJECTIVE: To detect the expression of long non-coding ribonucleic acid (lncRNA) RGMB-AS1 in papillary thyroid carcinoma (PTC) and to investigate its influences on PTC cell biological behaviors and its relevant molecular mechanisms. PATIENTS AND METHODS: The expression levels of lncRNA RGMB-AS1 in human PTC tissues, corresponding normal tissues, normal thyroid epithelial cells Nthyori3-1, human PTC cells TPC-1, BCPAP and K1 were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR)...
April 2018: European Review for Medical and Pharmacological Sciences
B Y Yang, Q Meng, Y Sun, L Gao, J X Yang
Glioma is among the most fatal and highly aggressive primary malignant tumors in the central nervous system. Small nucleolar RNA host gene 16 (SNHG16) is identified to play an oncogenic role in several cancers. However, the exact mechanism of SNHG16 action in the regulation of glioma development remains unknown. LncRNA SNHG16 was increased in glioma tissues and cells compared with normal brain tissues and cells. SNHG16 expression was correlated with the malignancy and poor prognosis of glioma patients. SNHG16 and E2F1 contained a binding site of miR-20a-5p...
March 2018: Journal of Biological Regulators and Homeostatic Agents
Veerabrahma Pratap Seshachalam, Karthik Sekar, Kam M Hui
BACKGROUND AND AIM: Hepatitis B virus, hepatitis C virus, alcoholic consumption and non-alcoholic fatty liver are the major known risk factors for Hepatocellular carcinoma (HCC). There have been very few studies comparing the underlying biological mechanisms associated with the different etiologies of HCC. In this study, we hypothesized the existence of different regulatory networks associated with different liver disease etiologies involved in hepatocarcinogenesis. METHODS: Using upstream regulatory analysis tool in ingenuity pathway analysis software, URs were predicted using differential expressed genes for HCC to facilitate the interrogation of global gene regulation...
April 19, 2018: Journal of Gastroenterology and Hepatology
Hyungkuen Kim, Sun Shin Yi, Hak-Kyo Lee, Tae-Hwe Heo, Sang-Kyu Park, Hyun Sik Jun, Ki Duk Song, Sung-Jo Kim
The vine stem of Spatholobus suberectus Dunn (SS) is used as a traditional herbal medicine in China. Chinese herbal medicines are well known as natural bioactive compounds that can be used as new medicines, and their antioxidant and anticancer effects have also been reported. This study aimed to examine the anticancer effect of a high-pressure hot-water SS extract on rat C6 glioma cells. The SS extract effectively suppressed the viability and proliferation of C6 glioma cells through an antioxidant effect. Reactive oxygen species (ROS) levels in cancer cells are higher than that in normal cells...
April 18, 2018: Nutrition and Cancer
Xiang-Long Zhuang, Rui-Ting Guan, Shi-Xin Wu, Dong Miu, Tong Qin
OBJECTIVE: To investigate the expression of E2F1 gene in patients with acute leukemia(AL) and its clinical significance. METHODS: Seventy-two AL patients treated in March 2015 -March 2016 in our hospital were selected, and 24 healthy people were selected as controls. RT-PCR and Western blot were applied to determine the level of E2F1 gene transcription and expression, and the statistical analysis was performed to reveal the clinical value of E2F1 gene. RESULTS: The relative expression levels of E2F1 gene and protein in bone marrow of AL patients was higher than that in control group (P<0...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Pilar López-Nieva, Pablo Fernández-Navarro, Concepción Vaquero-Lorenzo, María Villa-Morales, Osvaldo Graña-Castro, María Ángeles Cobos-Fernández, José Luis López-Lorenzo, Pilar Llamas, Laura González-Sanchez, Isabel Sastre, Marina Pollan, Marcos Malumbres, Javier Santos, José Fernández-Piqueras
BACKGROUND: Precursor T-cell lymphoblastic lymphomas (T-LBL) are rare aggressive hematological malignancies that mainly develop in children. As in other cancers, the loss of cell cycle control plays a prominent role in the pathogenesis in these malignancies that is primarily attributed to loss of CDKN2A (encoding protein p16INK4A). However, the impact of the deregulation of other genes such as CDKN1C, E2F1, and TP53 remains to be clarified. Interestingly, experiments in mouse models have proven that conditional T-cell specific deletion of Cdkn1c gene may induce a differentiation block at the DN3 to DN4 transition, and that the loss of this gene in the absence of Tp53 led to aggressive thymic lymphomas...
April 16, 2018: BMC Cancer
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