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https://www.readbyqxmd.com/read/27803714/senescence-associated-molecular-and-epigenetic-alterations-in-mesenchymal-stem-cell-cultures-from-amniotic-fluid-of-normal-and-fetus-affected-pregnancy
#1
Jūratė Savickienė, Sandra Baronaitė, Aistė Zentelytė, Gražina Treigytė, Rūta Navakauskienė
Human amniotic-fluid-derived mesenchymal stem cells (AF-MSCs) are interesting for their multilineage differentiation potential and wide range of therapeutic applications due to the ease of culture expansion. However, MSCs undergo replicative senescence. So far, the molecular mechanisms that underlie fetal diseases and cell senescence are still poorly understood. Here, we analyzed senescence-associated morphologic, molecular, and epigenetic characteristics during propagation of MSCs derived from AF of normal and fetus-affected pregnancy...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27793210/investigation-of-ezh2-pathways-for-novel-epigenetic-treatment-strategies-in-oropharyngeal-cancer
#2
Sherif Idris, Cameron Lindsay, Morris Kostiuk, Colin Andrews, David W J Côté, Daniel A O'Connell, Jeffrey Harris, Hadi Seikaly, Vincent L Biron
BACKGROUND: In recent decades, the incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been rising worldwide as a result of increasing oncogenic human papillomavirus (HPV) infections in the oropharynx. EZH2 is an epigenetic regulatory protein associated with tumor aggressiveness and negative survival outcomes in several human cancers. We aimed to determine the role of EZH2 as a potential therapeutic epigenetic target in HPV-positive and negative OPSCC. METHODS: The expression of EZH2 was measured by immunohistochemistry (IHC) and droplet digital PCR (ddPCR) in 2 HPV-positive and 2 HPV-negative cell lines...
October 28, 2016: Journal of Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/27719642/bona-fide-targets-of-deregulated-micrornas-in-non-small-cell-lung-cancer-as-tool-to-identify-novel-therapeutic-targets-a-review
#3
Monica Cipollini, Stefano Landi, Federica Gemignani
BACKGROUND: Non-small-cell lung cancer (NSCLC) is an aggressive neoplasm with a poor survival and novel therapies are urgently needed. The study of deregulated micro-RNAs (dereg-miRs) could constitute a strategy helping to detect specific genes playing a relevant role in the disease. Thus, the oncoproteins encoded by these genes could be exploited as novel therapeutic targets to be inhibited by small molecules, aptamers, or monoclonal antibodies. METHODS: The present review is focused on candidate genes having convincing biological evidences to be both bona fide targets for dereg-miRs and playing a role in NSCLC progression...
October 6, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27634879/large-variety-in-a-panel-of-human-colon-cancer-organoids-in-response-to-ezh2-inhibition
#4
Martijn Aj Koppens, Gergana Bounova, Paulien Cornelissen-Steijger, Nienke de Vries, Owen J Sansom, Lodewyk Fa Wessels, Maarten van Lohuizen
EZH2 inhibitors have gained great interest for their use as anti-cancer therapeutics. However, most research has focused on EZH2 mutant cancers and recently adverse effects of EZH2 inactivation have come to light. To determine whether colorectal cancer cells respond to EZH2 inhibition and to explore which factors influence the degree of response, we treated a panel of 20 organoid lines derived from human colon tumors with different concentrations of the EZH2 inhibitor GSK126. The resulting responses were associated with mutation status, gene expression and responses to other drugs...
September 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27610467/interfering-ezh2-expression-reverses-the-cisplatin-resistance-in-human-ovarian-cancer-by-inhibiting-autophagy
#5
Yang Sun, Long Jin, Jia-Hua Liu, Yu-Xia Sui, Li-Li Han, Xiao-Li Shen
We aimed to determine the effects of the inhibition of enhancer of zeste homolog 2 (EZH2) gene expression on the cisplatin resistance of the human ovarian cancer cell line, SKOV3/DDP, and to identify the underlying mechanisms. SKOV3/DDP cells were stably transfected with pSUPER-EZH2 (EZH2 RNA interference plasmid) or pcDNA3.1-EZH2 (EZH2 gene overexpression plasmid) using the lipofection method. Real-time fluorescence quantitative reverse transcription polymerase chain reaction and western blotting confirmed that EZH2 expression was downregulated in pSUPER-EZH2-transfected cells...
September 2016: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/27517917/the-antitumor-effect-of-metformin-is-mediated-by-mir-26a-in-breast-cancer
#6
Paula Cabello, Begoña Pineda, Eduardo Tormo, Ana Lluch, Pilar Eroles
Metformin, a drug approved for diabetes type II treatment, has been associated with a reduction in the incidence of breast cancer and metastasis and increased survival in diabetic breast cancer patients. High levels of miR-26a expression have been proposed as one of the possible mechanisms for this effect; likewise, this miRNA has also been associated with survival/apoptosis processes in breast cancer. Our aim was to evaluate if miR-26a and some of its targets could mediate the effect of metformin in breast cancer...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27472460/ezh2-mediated-puma-gene-repression-regulates-non-small-cell-lung-cancer-cell-proliferation-and-cisplatin-induced-apoptosis
#7
Haidan Liu, Wei Li, Xinfang Yu, Feng Gao, Zhi Duan, Xiaolong Ma, Shiming Tan, Yunchang Yuan, Lijun Liu, Jian Wang, Xinmin Zhou, Yifeng Yang
Polycomb group (PcG) proteins are highly conserved epigenetic effectors that maintain the silenced state of genes. EZH2 is the catalytic core and one of the most important components of the polycomb repressive complex 2 (PRC2). In non-small cell lung cancer (NSCLC) cells and primary lung tumors, we found that PRC2 components, including EZH2, are overexpressed. High levels of EZH2 protein were associated with worse overall survival rate in NSCLC patients. RNA interference mediated attenuation of EZH2 expression blunted the malignant phenotype in this setting, exerting inhibitory effects on cell proliferation, anchorage-independent growth, and tumor development in a xenograft mouse model...
July 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27461342/hypomethylation-coordinates-antagonistically-with-hypermethylation-in-cancer-development-a-case-study-of-leukemia
#8
Garima Kushwaha, Mikhail Dozmorov, Jonathan D Wren, Jing Qiu, Huidong Shi, Dong Xu
BACKGROUND: Methylation changes are frequent in cancers, but understanding how hyper- and hypomethylated region changes coordinate, associate with genomic features, and affect gene expression is needed to better understand their biological significance. The functional significance of hypermethylation is well studied, but that of hypomethylation remains limited. Here, with paired expression and methylation samples gathered from a patient/control cohort, we attempt to better characterize the gene expression and methylation changes that take place in cancer from B cell chronic lymphocyte leukemia (B-CLL) samples...
2016: Human Genomics
https://www.readbyqxmd.com/read/27432063/over-expression-of-mir-200c-suppresses-invasion-and-restores-methotrexate-sensitivity-in-lung-cancer-a549-cells
#9
Wulin Shan, Xiaolei Zhang, Ming Li, Fang Deng, Jing Zhang
MicroRNAs have become recognized as key players in the development of malignancy. MiR-200c can function as a tumor suppressor gene. However, the effect of miR-200c on methotrexate resistance remains unclear to date. This study aims to evaluate the function of miR-200c in lung cancer A549 cells. The data presented in our study demonstrated that the expression of miR-200c was down-regulated in methotrexate-resistant A549 cells. Over expression of miR-200c could significantly inhibit cell proliferation, induce G0/G1 cell cycle arrest and induce cell apoptosis...
November 30, 2016: Gene
https://www.readbyqxmd.com/read/27323178/expression-and-clinical-implications-of-enhancer-of-zeste-homolog-2-and-p53-protein-in-squamous-cell-carcinoma-and-precancerous-lesions-in-the-cervix
#10
H M Zhang, S Q Chen, S Z Yao
We investigated the expression and clinical implications of enhancer of Zeste homolog 2 (EZH2) and p53 protein in cervical squamous cell carcinoma (SCC) and precancerous lesions. EZH2 and p53 expressions in SCC (168), cervical intraepithelial neoplasia (CIN)-I (19), CIN-II (35), and normal tissues (30) were detected by streptavidin-peroxidase-conjugation. The correlation between co-expression of EZH2 and p53 protein and the clinic pathological features and prognosis of SCC were discussed. The positive expression rates of EZH2 and p53 were 6...
2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27247549/identification-of-differentially-expressed-genes-associated-with-the-enhancement-of-x-ray-susceptibility-by-rita-in-a-hypopharyngeal-squamous-cell-carcinoma-cell-line-fadu
#11
Jinwei Luan, Xianglan Li, Rutao Guo, Shanshan Liu, Hongyu Luo, Qingshan You
BACKGROUND: Next generation sequencing and bio-informatic analyses were conducted to investigate the mechanism of reactivation of p53 and induction of tumor cell apoptosis (RITA)-enhancing X-ray susceptibility in FaDu cells. MATERIALS AND METHODS: The cDNA was isolated from FaDu cells treated with 0 X-ray, 8 Gy X-ray, or 8 Gy X-ray + RITA. Then, cDNA libraries were created and sequenced using next generation sequencing, and each assay was repeated twice. Subsequently, differentially expressed genes (DEGs) were identified using Cuffdiff in Cufflinks and their functions were predicted by pathway enrichment analyses...
June 1, 2016: Radiology and Oncology
https://www.readbyqxmd.com/read/27149985/ezh2-is-overexpressed-in-adrenocortical-carcinoma-and-is-associated-with-disease-progression
#12
Coralie Drelon, Annabel Berthon, Mickael Mathieu, Bruno Ragazzon, Rork Kuick, Houda Tabbal, Amandine Septier, Stéphanie Rodriguez, Marie Batisse-Lignier, Isabelle Sahut-Barnola, Typhanie Dumontet, Jean-Christophe Pointud, Anne-Marie Lefrançois-Martinez, Silvère Baron, Thomas J Giordano, Jérôme Bertherat, Antoine Martinez, Pierre Val
Adrenal Cortex Carcinoma (ACC) is an aggressive tumour with poor prognosis. Common alterations in patients include constitutive WNT/β-catenin signalling and overexpression of the growth factor IGF2. However, the combination of both alterations in transgenic mice is not sufficient to trigger malignant tumour progression, suggesting that other alterations are required to allow development of carcinomas. Here, we have conducted a study of publicly available gene expression data from three cohorts of ACC patients to identify relevant alterations...
May 5, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27135738/an-oncogenic-ezh2-mutation-induces-tumors-through-global-redistribution-of-histone-3-lysine-27-trimethylation
#13
George P Souroullas, William R Jeck, Joel S Parker, Jeremy M Simon, Jie-Yu Liu, Joshiawa Paulk, Jessie Xiong, Kelly S Clark, Yuri Fedoriw, Jun Qi, Christin E Burd, James E Bradner, Norman E Sharpless
B cell lymphoma and melanoma harbor recurrent mutations in the gene encoding the EZH2 histone methyltransferase (EZH2), but the carcinogenic role of these mutations is unclear. Here we describe a mouse model in which the most common somatic Ezh2 gain-of-function mutation (EZH2(Y646F) in human; Ezh2(Y641F) in mouse) is conditionally expressed. Expression of Ezh2(Y641F) in mouse B cells or melanocytes caused high-penetrance lymphoma or melanoma, respectively. Overexpression of the anti-apoptotic protein Bcl2, but not the oncoprotein Myc, or loss of the tumor suppressor protein p53 (encoded by Trp53 in mice) further accelerated lymphoma progression...
June 2016: Nature Medicine
https://www.readbyqxmd.com/read/27129219/hbp1-mediated-regulation-of-p21-protein-through-the-mdm2-p53-and-tcf4-ezh2-pathways-and-its-impact-on-cell-senescence-and-tumorigenesis
#14
Yifan Chen, Kewu Pan, Pingzhang Wang, Zhengyi Cao, Weibin Wang, Shuya Wang, Ningguang Hu, Junhui Xue, Hui Li, Wei Jiang, Gang Li, Xiaowei Zhang
The activity of the CDK inhibitor p21 is associated with diverse biological activities, including cell proliferation, senescence, and tumorigenesis. However, the mechanisms governing transcription of p21 need to be extensively studied. In this study, we demonstrate that the high-mobility group box-containing protein 1 (HBP1) transcription factor is a novel activator of p21 that works as part of a complex mechanism during senescence and tumorigenesis. We found that HBP1 activates the p21 gene through enhancing p53 stability by inhibiting Mdm2-mediated ubiquitination of p53, a well known positive regulator of p21...
June 10, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27066096/high-ezh2-protein-expression-is-associated-with-poor-overall-survival-in-patients-with-luminal-a-breast-cancer
#15
Si-Hyong Jang, Jong Eun Lee, Mee-Hye Oh, Ji-Hye Lee, Hyun Deuk Cho, Kyung-Ju Kim, Sung Yong Kim, Sun Wook Han, Han Jo Kim, Sang Byung Bae, Hyun Ju Lee
PURPOSE: The enhancer of zeste homologue 2 (EZH2) is a catalytic subunit of the polycomb repressive complex 2, a highly conserved histone methyltransferase. EZH2 overexpression has been implicated in various malignancies, including breast cancer, where is associated with poor outcomes. This study aims to clarify nuclear EZH2 expression levels in breast cancers using immunohistochemistry (IHC) and correlate these findings with clinicopathologic variables, including prognostic significance...
March 2016: Journal of Breast Cancer
https://www.readbyqxmd.com/read/27050973/relationship-between-the-expression-of-notch1-and-ezh2-and-the-prognosis-of-breast-invasive-ductal-carcinoma
#16
L Zhao, Q Y Zhang, X Luan, X Huang, S Zhao, H Zhao
We determined whether the coexpression of Notch1 and EZH2 influences the progression and prognosis of breast invasive ductal carcinoma. Using the χ(2) test, a significant difference was found between high and low expression of Notch1 in terms of lymph node, hormone receptor, and p53 expression (P < 0.05). Moreover, a significant difference was found between high and low expression of EZH2 in terms of tumor size, histologic grade, hormone receptor, and expression of Ki67 (P < 0.05). Using Pearson correlation analysis, we found a significant positive correlation between Notch1 and EZH2 expression in the tissue samples of breast invasive ductal carcinoma (P = 0...
2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/26980915/tumor-biomarkers-in-spindle-cell-variant-squamous-cell-carcinoma-of-the-head-and-neck
#17
Andrew J Rosko, Andrew C Birkeland, Kevin F Wilson, Daniel G Muenz, Emily Bellile, Carol R Bradford, Jonathan B McHugh, Matthew E Spector
OBJECTIVE: To determine biomarkers of recurrence and survival in patients with spindle cell variant squamous cell carcinoma (SpSCC) of the head and neck. STUDY DESIGN: Retrospective case control study. SETTING: Tertiary academic center. SUBJECTS AND METHODS: Thirty-two SpSCC patients (mean age, 68.8) between 1987 and 2009 were identified and reviewed. A tissue microarray (TMA) was constructed from tumor specimens. Tumor biomarkers under study included p16, epidermal growth factor receptor (EGFR), p53, EZH2, cyclin D1, CD104, HGFa, p21, and cMET...
July 2016: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/26973857/ezh2-inhibition-re-sensitizes-multidrug-resistant-b-cell-lymphomas-to-etoposide-mediated-apoptosis
#18
Matthew Smonskey, Elena Lasorsa, Spencer Rosario, Jason S Kirk, Francisco J Hernandez-Ilizaliturri, Leigh Ellis
Reactivation of apoptotic pathways is an attractive strategy for patients with treatment-resistant B-cell lymphoma. The tumor suppressor, p53 is central for apoptotic response to multiple DNA damaging agents used to treat aggressive B-cell lymphomas, including etoposide. It has been demonstrated that etoposide induced DNA damage and therapeutic efficacy is enhanced by combination with inhibitors of the histone methyltransferase, enhancer of zeste homolog 2 (EZH2). Further, EZH2 was identified to regulate cell fate decisions in response to DNA damage...
2016: Oncoscience
https://www.readbyqxmd.com/read/26908628/long-noncoding-rna-pvt1-promotes-non-small-cell-lung-cancer-cell-proliferation-through-epigenetically-regulating-lats2-expression
#19
Li Wan, Ming Sun, Guo-Jian Liu, Chen-Chen Wei, Er-Bao Zhang, Rong Kong, Tong-Peng Xu, Ming-De Huang, Zhao-Xia Wang
Long noncoding RNAs (lncRNA) are a novel class of transcripts with no protein coding capacity, but with diverse functions in cancer cell proliferation, apoptosis, and metastasis. The lncRNA PVT1 is 1,716 nt in length and located in the chr8q24.21 region, which also contains the myelocytomatosis (MYC) oncogene. Previous studies demonstrated that MYC promotes PVT1 expression in primary human cancers. However, the expression pattern and potential biologic function of PVT1 in non-small cell lung cancer (NSCLC) is still unclear...
May 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/26773040/diffuse-large-b-cell-lymphoma-patient-derived-xenograft-models-capture-the-molecular-and-biological-heterogeneity-of-the-disease
#20
Bjoern Chapuy, Hongwei Cheng, Akira Watahiki, Matthew D Ducar, Yuxiang Tan, Linfeng Chen, Margaretha G M Roemer, Jing Ouyang, Amanda L Christie, Liye Zhang, Daniel Gusenleitner, Ryan P Abo, Pedro Farinha, Frederike von Bonin, Aaron R Thorner, Heather H Sun, Randy D Gascoyne, Geraldine S Pinkus, Paul van Hummelen, Gerald G Wulf, Jon C Aster, David M Weinstock, Stefano Monti, Scott J Rodig, Yuzhuo Wang, Margaret A Shipp
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease defined by transcriptional classifications, specific signaling and survival pathways, and multiple low-frequency genetic alterations. Preclinical model systems that capture the genetic and functional heterogeneity of DLBCL are urgently needed. Here, we generated and characterized a panel of large B-cell lymphoma (LBCL) patient-derived xenograft (PDX) models, including 8 that reflect the immunophenotypic, transcriptional, genetic, and functional heterogeneity of primary DLBCL and 1 that is a plasmablastic lymphoma...
May 5, 2016: Blood
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