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Cancer progression chromatin

Chunqing Dou, Liyuan Sun, Xin Jin, Mingming Han, Bao Zhang, Xian Jiang, Jinyong Lv, Tao Li
Long non-coding RNAs (lncRNAs) play key roles in cancer initiation and progression. The aim was to investigate the biological functions and clinical significance of long non-coding RNA CARLo-5 in hepatocellular carcinoma (HCC). QRT-PCR was performed to investigate CARLo-5 expression in HCC tissues and cells. Kaplan-Meier curve and multivariate analysis validated the association between CARLo-5 expression and overall survival (OS) in HCC patients. Cell proliferation and invasion was performed by CCK8 cell proliferation, cell colony formation and transwell invasion assays...
September 19, 2017: Oncotarget
Amaury E Fernández-Montalván, Markus Berger, Benno Kuropka, Seong Joo Koo, Volker Badock, Joerg Weiske, Vera Puetter, Simon J Holton, Detlef Stöckigt, Antonius Ter Laak, Paolo A Centrella, Matthew A Clark, Christoph E Dumelin, Eric A Sigel, Holly H Soutter, Dawn M Troast, Ying Zhang, John W Cuozzo, Anthony D Keefe, Didier Roche, Vincent Rodeschini, Apirat Chaikuad, Laura Díaz-Sáez, James M Bennett, Oleg Fedorov, Kilian V M Huber, Jan Huebner, Hilmar Weinmann, Ingo V Hartung, Matyas Gorjanacz
ATAD2 (ANCCA) is an epigenetic regulator and transcriptional co-factor, whose over-expression has been linked to the progress of various cancer types. Here we report a DNA-encoded library screen leading to the discovery of BAY-850, a potent and isoform selective inhibitor that specifically induces ATAD2 bromodomain dimerization, and prevents interactions with acetylated histones in vitro, as well as with chromatin in cells. These features qualify BAY-850 as chemical probe to explore ATAD2 biology.
October 18, 2017: ACS Chemical Biology
Reinhard H Dammann, Antje M Richter, Adriana P Jiménez, Michelle Woods, Miriam Küster, Chamindri Witharana
Epigenetic inactivation of tumor suppressor genes (TSG) is a fundamental event in the pathogenesis of human cancer. This silencing is accomplished by aberrant chromatin modifications including DNA hypermethylation of the gene promoter. One of the most frequently hypermethylated TSG in human cancer is the Ras Association Domain Family 1A (RASSF1A) gene. Aberrant methylation of RASSF1A has been reported in melanoma, sarcoma and carcinoma of different tissues. RASSF1A hypermethylation has been correlated with tumor progression and poor prognosis...
October 17, 2017: International Journal of Molecular Sciences
M Janaki Ramaiah, Shaik Mohammad Naushad, P O N Lavanya, A Gayatri, S Vaishnave, Manika Pal-Bhadra
MicroRNAs (miRNAs) are a class of small, non-coding RNAs that are involved in the regulation of gene expression at the post-transcriptional level. MicroRNAs play an important role in cancer cell proliferation, survival and apoptosis. Epigenetic modifiers regulate the microRNA expression. Among the epigenetic players, histone deacetylases (HDACs) function as the key regulators of microRNA expression. Epigenetic machineries such as DNA and histone modifying enzymes and various microRNAs have been identified as the important contributors in cancer initiation and progression...
October 13, 2017: Gene
Yiqun Jiang, Yuchen He, Shuang Liu, Yongguang Tao
No abstract text is available yet for this article.
October 16, 2017: Chinese Journal of Cancer
Saurabh Pandey, Erle S Robertson
In cancer progression, metastasis is a major cause of poor survival of patients and can be targeted for therapeutic interventions. The first discovered metastatic-suppressor Nm23-H1 possesses nucleoside diphosphate kinase, histidine kinase, and DNase activity as a broad-spectrum enzyme. Recent advances in cancer metastasis have opened new ways for the development of therapeutic molecular approaches. In this review, we provide a summary of the current understanding of Nm23/NDPKs in the context of viral oncogenesis...
October 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
Dylan M Glubb, Sharon E Johnatty, Michael C J Quinn, Tracy A O'Mara, Jonathan P Tyrer, Bo Gao, Peter A Fasching, Matthias W Beckmann, Diether Lambrechts, Ignace Vergote, Digna R Velez Edwards, Alicia Beeghly-Fadiel, Javier Benitez, Maria J Garcia, Marc T Goodman, Pamela J Thompson, Thilo Dörk, Matthias Dürst, Francesmary Modungo, Kirsten Moysich, Florian Heitz, Andreas du Bois, Jacobus Pfisterer, Peter Hillemanns, Beth Y Karlan, Jenny Lester, Ellen L Goode, Julie M Cunningham, Stacey J Winham, Melissa C Larson, Bryan M McCauley, Susanne Krüger Kjær, Allan Jensen, Joellen M Schildkraut, Andrew Berchuck, Daniel W Cramer, Kathryn L Terry, Helga B Salvesen, Line Bjorge, Penny M Webb, Peter Grant, Tanja Pejovic, Melissa Moffitt, Claus K Hogdall, Estrid Hogdall, James Paul, Rosalind Glasspool, Marcus Bernardini, Alicia Tone, David Huntsman, Michelle Woo, Aocs Group, Anna deFazio, Catherine J Kennedy, Paul D P Pharoah, Stuart MacGregor, Georgia Chenevix-Trench
We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that MEF2D and ZNF100 are targets of candidate outcome variants at 1q22 and 19p12, respectively. At 19p12, the chromatin interaction of a putative regulatory element with the ZNF100 promoter region correlated with candidate outcome variants...
September 12, 2017: Oncotarget
Dongbo Liu, Hongping Miao, Yuanyin Zhao, Xia Kang, Shenglan Shang, Wei Xiang, Rongchen Shi, Along Hou, Rui Wang, Kun Zhao, Yingzhe Liu, Yue Ma, Huan Luo, Hongming Miao, Fengtian He
BACKGROUND: Chronic inflammation is causally linked to the carcinogenesis and progression of most solid tumors. LPTS is a well-identified tumor suppressor by inhibiting telomerase activity and cancer cell growth. However, whether and how LPTS is regulated by inflammation signaling is still incompletely elucidated. METHODS: Real-time PCR and western blotting were used to determine the expression of p65 and LPTS. Reporter gene assay, electrophoretic mobility shift assay and chromatin immunoprecipitation were performed to decipher the regulatory mechanism between p65 and LPTS...
October 10, 2017: Cell Communication and Signaling: CCS
L-F Wang, Y-S Liu, B Yang, P Li, X-S Cheng, C-X Xiao, J-J Liu, S Li, J-L Ren, B Guleng
Mindin, a secreted, highly conserved extracellular matrix (ECM) protein, exerts a broad spectrum of effects on the innate immune system. However, its function in colorectal cancer (CRC) progression is not well established, and its upstream regulation mechanisms remain unclear. Contrary to previous reports, this study used two different enzyme-linked immunosorbent assay (ELISA) kits to show that the serum level of mindin was significantly decreased in CRC patients and that this decreased level is more significantly associated with the early stages of the disease...
October 9, 2017: Oncogene
Lei Guo, Jianjiang Zheng, Tao Yu, Yuequan Liu, Lukun Duo
Special AT‑rich sequence‑binding protein 1 (SATB1) is a master chromatin organizer which has been reported to be implicated in tumor progression in breast and lung cancer. However, its functions in pancreatic tumorigenesis have yet to be elucidated. In the present study, the involvement of SATB1 in pancreatic cancer development was investigated in human BxPC‑3 pancreatic adenocarcinoma cells. Short hairpin (sh)RNA was used to stably downregulate SATB1 expression, and functional assays, including cell proliferation, colony formation, soft agar and migration assays, were performed in vitro...
October 2, 2017: Molecular Medicine Reports
Leonel Armas-López, Patricia Piña-Sánchez, Oscar Arrieta, Enrique Guzman de Alba, Blanca Ortiz-Quintero, Patricio Santillán-Doherty, David C Christiani, Joaquín Zúñiga, Federico Ávila-Moreno
Several homeobox-related gene (HOX) transcription factors such as mesenchyme HOX-2 (MEOX2) have previously been associated with cancer drug resistance, malignant progression and/or clinical prognostic responses in lung cancer patients; however, the mechanisms involved in these responses have yet to be elucidated. Here, an epigenomic strategy was implemented to identify novel MEOX2 gene promoter transcription targets and propose a new molecular mechanism underlying lung cancer drug resistance and poor clinical prognosis...
September 15, 2017: Oncotarget
Laura Gil, Concetta Federico, Fernando Pinedo, Francesca Bruno, Ana B Rebolledo, Juan J Montoya, Isabel M Olazabal, Isidre Ferrer, Salvatore Saccone
Tau protein is characterized by a complex pattern of phosphorylation and is localized in the cytoplasm and nucleus in both neuronal and non-neuronal cells. Human AT100 nuclear tau, endowed by phosphorylation in Thr212/Ser214, was recently shown to decline in cornus ammonis 1 (CA1) and dentate gyrus (DG) in Alzheimer's disease (AD), but a defined function for this nuclear tau remains unclear. Here we show that AT100 progressively increases in the nuclei of neuronal and non-neuronal cells during aging, and decreases in the more severe AD stages, as recently shown, and in cancer cells (colorectal adenocarcinoma and breast cancer)...
September 30, 2017: Brain Research
Tonghai Huang, Guangsuo Wang, Lin Yang, Bin Peng, Yuxin Wen, Guanggui Ding, Zheng Wang
Lung cancer is the leading cause of cancer-related death worldwide. Despite the advancement in surgery and chemotherapy, the prognosis of patients with advanced lung cancer is still poor. Yin Yang-1 (YY1) is a multifunctional transcription factor that exhibits positive and negative control on a large number of cellular and viral genes. In this study, we showed that the expression of YY1 is upregulated in lung cancer tissues as compared to adjacent normal tissues. Patients with higher expression of YY1 had larger tumor size, poor differentiation, higher TNM stage, and lymph node metastasis...
October 3, 2017: DNA and Cell Biology
Nicola Cornella, Toma Tebaldi, Lisa Gasperini, Jarnail Singh, Richard A Padgett, Annalisa Rossi, Paolo Macchi
The heterogeneous nuclear ribonucleoproteins (hnRNPs) form a large family of RNA-binding proteins that exert numerous functions in RNA metabolism. RALY is a member of the hnRNP family that binds poly-U rich elements within several RNAs and regulates the expression of specific transcripts. RALY is upregulated in different types of cancer, and its downregulation impairs cell cycle progression. However, RALY's role in regulating RNA levels remains elusive. Here, we show that numerous genes coding for factors involved in transcription and cell cycle regulation exhibit an altered expression in RALY-downregulated HeLa cells, consequently causing impairments in transcription, cell proliferation and cell cycle progression...
September 27, 2017: Journal of Biological Chemistry
Priyanka Bhateja, Afshin Dowlati, Neelesh Sharma
Introduction Preclinical data suggest quinacrine acts as an inhibitor of FACT (facilitates chromatin transcription) complex, which may play a role in TKI (tyrosine kinase inhibitor) resistance. The aim of this Phase I study was to study the safety and assess the maximum tolerated dose of quinacrine in combination with erlotinib in non small cell lung cancer (NSCLC). Methods This was a phase I study with standard 3 + 3 dose escalation design with the primary aim of determining the maximum tolerated dose. Two of 3 patients enrolled at dose level 1 experienced dose limiting toxicity (DLT)...
October 2, 2017: Investigational New Drugs
Luciane T Kagohara, Genevieve L Stein-O'Brien, Dylan Kelley, Emily Flam, Heather C Wick, Ludmila V Danilova, Hariharan Easwaran, Alexander V Favorov, Jiang Qian, Daria A Gaykalova, Elana J Fertig
Cancer is a complex disease, driven by aberrant activity in numerous signaling pathways in even individual malignant cells. Epigenetic changes are critical mediators of these functional changes that drive and maintain the malignant phenotype. Changes in DNA methylation, histone acetylation and methylation, noncoding RNAs, posttranslational modifications are all epigenetic drivers in cancer, independent of changes in the DNA sequence. These epigenetic alterations were once thought to be crucial only for the malignant phenotype maintenance...
August 11, 2017: Briefings in Functional Genomics
Yiming Ma, Wei Yu, Anju Shrivastava, Farzad Alemi, Kamani Lankachandra, Rakesh K Srivastava, Sharmila Shankar
Sonic hedgehog pathway is highly activated in pancreatic cancer stem cells (CSC) which play crucial roles in cancer initiation, progression and metastasis. However, the molecular mechanisms by which sanguinarine regulates pancreatic CSC characteristics is not well understood. The objectives of this study were to examine the molecular mechanisms by which sanguinarine regulates pancreatic CSC characteristics. Sanguinarine inhibited cell proliferation and colony formation and induced apoptosis through oxidative damage...
September 5, 2017: Carcinogenesis
David J Cantor, Gregory David
Sin3B serves as a scaffold for chromatin-modifying complexes that repress gene transcription to regulate distinct biological processes. Sin3B-containing complexes are critical for cell cycle withdrawal, and abrogation of Sin3B-dependent cell cycle exit impacts tumor progression. Areas covered: In this review, we discuss the biochemical characteristics of Sin3B-containing complexes and explore how these complexes regulate gene transcription. We focus on how Sin3B-containing complexes, through the association of the Rb family of proteins, repress the expression of E2F target genes during quiescence, differentiation, and senescence...
September 28, 2017: Expert Opinion on Therapeutic Targets
F J Guo, Y P Shao, Y P Wang, Y M Jin, S S Liu, Q Y Wang
The molecular mechanisms underlying regulation of vascular endothelial growth factor (VEGF) in epithelial ovarian cancer (EOC) remain poorly defined. VEGF, a potent angiogenic factor, is up-regulated in a variety of cancers and contributes to angiogenesis in tumor tissues. The level of VEGF correlates with progression of malignancy. We previously reported that miR-92 is abnormally elevated in the plasma of EOC patients. Here, we tested the hypothesis that miR-92 inhibits von Hippel-Lindau gene product (VHL), a tumor suppressor gene, and in turn de-represses HIF-1α, a known key transcription factor for VEGF, to stimulate VEGF expression...
July 2017: Journal of Biological Regulators and Homeostatic Agents
Ousman Tamgue, Ming Lei
Background: Triptolide is a medicinal herb-derived diterpene triepoxide with potent anti-tumor activity, mainly ,correlated with its ability to inhibit and inactivate subunits of RNA polymerase II, thereby suppressing global gene transcription. Epigenetic imbalance including histone methylation are well known to play important roles in prostate cancer (PCa) onset and progression. The goal of this study was to investigate whether triptolide might exert anti-PCa influence by reshaping the histone methylation landscape...
September 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
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