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https://www.readbyqxmd.com/read/28821760/a-database-of-breast-oncogenic-specific-sirnas
#1
Atul Tyagi, Manoj Semwal, Ashok Sharma
Breast cancer is a serious problem causing the death of women across the world. At present, one of the major challenges is to design drugs to target breast cancer specific gene(s). RNA interference (RNAi) is an important technique for targeted gene silencing that may lead to promising novel therapeutic strategies for breast cancer. Therefore, identification of such molecules having high oncogene specificity is the need of the hour. Here, we have developed a database named as Breast Oncogenic Specific siRNAs (BOSS, http://bioinformatics...
August 18, 2017: Scientific Reports
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
#2
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/28771721/the-ubiquitin-ligase-trim56-inhibits-ovarian-cancer-progression-by-targeting-vimentin
#3
Lei Zhao, Ping Zhang, Xiao-Jie Su, Bing Zhang
Tumor metastasis is responsible for 90% of all cancer-related deaths. Epithelial to mesenchymal transition (EMT) is an important prerequisite for tumor metastasis. One of the important mediators of EMT and cancer progression in ovarian cancer is the vimentin protein. The objective of the current study was to evaluate the molecular mechanism that regulates vimentin expression in ovarian cancer cells. Vimentin was robustly induced in the ovarian cancer cell line SKOV-3 compared to normal ovarian epithelial cell line Moody and the induction was not due to transcriptional upregulation...
August 3, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28770278/an-unbiased-in-vivo-functional-genomics-screening-approach-in-mice-identifies-novel-tumor-cell-based-regulators-of-immune-rejection
#4
Casey W Shuptrine, Reham Ajina, Elana J Fertig, Sandra A Jablonski, H Kim Lyerly, Zachary C Hartman, Louis M Weiner
The clinical successes of immune checkpoint therapies for cancer make it important to identify mechanisms of resistance to anti-tumor immune responses. Numerous resistance mechanisms have been identified employing studies of single genes or pathways, thereby parsing the tumor microenvironment complexity into tractable pieces. However, this limits the potential for novel gene discovery to in vivo immune attack. To address this challenge, we developed an unbiased in vivo genome-wide RNAi screening platform that leverages host immune selection in strains of immune-competent and immunodeficient mice to select for tumor cell-based genes that regulate in vivo sensitivity to immune attack...
August 2, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28769576/foxj2-overexpression-is-associated-with-poor-prognosis-progression-and-metastasis-in-nasopharyngeal-carcinoma
#5
Ying Shan, Tao Chang, Si Shi, Mingming Tang, Lili Bao, Li Li, Bo You, Yiwen You
Foxj2, a novel member of Forkhead box family, has been reported to play an important role in tumorigenesis, progression, and metastasis of certain cancers. However, the expression status and effects of Foxj2 on nasopharyngeal carcinoma (NPC) progression and metastasis remain debated. In this study, we first examined the expression of Foxj2 in NPC by immunohistochemistry and Western blotting analysis. We confirmed significantly elevated expression of Foxj2 in NPC tissues and cell lines. Next, the relationships between Foxj2 expression levels and the clinicopathological factors were investigated...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28766011/rnai-screen-identifies-essential-regulators-of-human-brain-metastasis-initiating-cells
#6
Mohini Singh, Chitra Venugopal, Tomas Tokar, Kevin R Brown, Nicole McFarlane, David Bakhshinyan, Thusyanth Vijayakumar, Branavan Manoranjan, Sujeivan Mahendram, Parvez Vora, Maleeha Qazi, Manvir Dhillon, Amy Tong, Kathrin Durrer, Naresh Murty, Robin Hallet, John A Hassell, David R Kaplan, Jean-Claude Cutz, Igor Jurisica, Jason Moffat, Sheila K Singh
Brain metastases (BM) are the most common brain tumor in adults and are a leading cause of cancer mortality. Metastatic lesions contain subclones derived from their primary lesion, yet their functional characterization is limited by a paucity of preclinical models accurately recapitulating the metastatic cascade, emphasizing the need for a novel approach to BM and their treatment. We identified a unique subset of stem-like cells from primary human patient brain metastases, termed brain metastasis-initiating cells (BMICs)...
August 1, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28761362/targeted-tpx2-increases-chromosome-missegregation-and-suppresses-tumor-cell-growth-in-human-prostate-cancer
#7
Hung-Wei Pan, Hsing-Hao Su, Chao-Wen Hsu, Guan-Jin Huang, Tony Tong-Lin Wu
Prostate cancer is a complex disease that can be relatively harmless or extremely aggressive. Although androgen-deprivation therapy is a commonly used treatment for men with prostate cancer, the adverse effects can be detrimental to patient health and quality of life. Therefore, identifying new target genes for tumor growth will enable the development of novel therapeutic intervention. TPX2 plays a critical role in chromosome segregation machinery during mitosis. Low rates of chromosome missegregation can promote tumor development, whereas higher levels might promote cell death and suppress tumorigenesis...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28754871/mir-34a-modulates-ionizing-radiation-induced-senescence-in-lung-cancer-cells
#8
Xiaoyuan He, Aimin Yang, Daniel G McDonald, Ellen C Riemer, Kenneth N Vanek, Bradley A Schulte, Gavin Y Wang
MicroRNAs (miRNAs) are a new class of gene expression regulators that have been implicated in tumorigenesis and modulation of the responses to cancer treatment including that of human non-small cell lung cancer (NSCLC). However, the role of miR-34a in ionizing radiation (IR)-induced senescence in NSCLC cells remains poorly understood. Here we report that IR-induced premature senescence correlates with upregulation of miR-34a expression in NSCLC cells. Ectopic overexpression of miR-34a by transfection with synthetic miR-34a mimics markedly enhances IR-induced senescence, whereas inhibition of miR-34a by transfection with a synthetic miR-34a inhibitor attenuates IR-induced senescence...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28754120/nano-based-delivery-of-rnai-in-cancer-therapy
#9
REVIEW
Yong Xin, Min Huang, Wen Wen Guo, Qian Huang, Long Zhen Zhang, Guan Jiang
BACKGROUND: RNA interference (RNAi), a newly developed method in which RNA molecules inhibit gene expression, has recently received considerable research attention. In the development of RNAi-based therapies, nanoparticles, which have distinctive size effects along with facile modification strategies and are capable of mediating effective RNAi with targeting potential, are attracting extensive interest. OBJECTIVE: This review presents an overview of the mechanisms of RNAi molecules in gene therapy and the different nanoparticles used to deliver RNAi molecules; briefly describes the current uses of RNAi in cancer therapy along with the nano-based delivery of RNA molecules in previous studies; and highlights some other carriers that have been applied in clinical settings...
July 28, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28753431/project-drive-a-compendium-of-cancer-dependencies-and-synthetic-lethal-relationships-uncovered-by-large-scale-deep-rnai-screening
#10
E Robert McDonald, Antoine de Weck, Michael R Schlabach, Eric Billy, Konstantinos J Mavrakis, Gregory R Hoffman, Dhiren Belur, Deborah Castelletti, Elizabeth Frias, Kalyani Gampa, Javad Golji, Iris Kao, Li Li, Philippe Megel, Thomas A Perkins, Nadire Ramadan, David A Ruddy, Serena J Silver, Sosathya Sovath, Mark Stump, Odile Weber, Roland Widmer, Jianjun Yu, Kristine Yu, Yingzi Yue, Dorothee Abramowski, Elizabeth Ackley, Rosemary Barrett, Joel Berger, Julie L Bernard, Rebecca Billig, Saskia M Brachmann, Frank Buxton, Roger Caothien, Justina X Caushi, Franklin S Chung, Marta Cortés-Cros, Rosalie S deBeaumont, Clara Delaunay, Aurore Desplat, William Duong, Donald A Dwoske, Richard S Eldridge, Ali Farsidjani, Fei Feng, JiaJia Feng, Daisy Flemming, William Forrester, Giorgio G Galli, Zhenhai Gao, François Gauter, Veronica Gibaja, Kristy Haas, Marc Hattenberger, Tami Hood, Kristen E Hurov, Zainab Jagani, Mathias Jenal, Jennifer A Johnson, Michael D Jones, Avnish Kapoor, Joshua Korn, Jilin Liu, Qiumei Liu, Shumei Liu, Yue Liu, Alice T Loo, Kaitlin J Macchi, Typhaine Martin, Gregory McAllister, Amandine Meyer, Sandra Mollé, Raymond A Pagliarini, Tanushree Phadke, Brian Repko, Tanja Schouwey, Frances Shanahan, Qiong Shen, Christelle Stamm, Christine Stephan, Volker M Stucke, Ralph Tiedt, Malini Varadarajan, Kavitha Venkatesan, Alberto C Vitari, Marco Wallroth, Jan Weiler, Jing Zhang, Craig Mickanin, Vic E Myer, Jeffery A Porter, Albert Lai, Hans Bitter, Emma Lees, Nicholas Keen, Audrey Kauffmann, Frank Stegmeier, Francesco Hofmann, Tobias Schmelzle, William R Sellers
Elucidation of the mutational landscape of human cancer has progressed rapidly and been accompanied by the development of therapeutics targeting mutant oncogenes. However, a comprehensive mapping of cancer dependencies has lagged behind and the discovery of therapeutic targets for counteracting tumor suppressor gene loss is needed. To identify vulnerabilities relevant to specific cancer subtypes, we conducted a large-scale RNAi screen in which viability effects of mRNA knockdown were assessed for 7,837 genes using an average of 20 shRNAs per gene in 398 cancer cell lines...
July 27, 2017: Cell
https://www.readbyqxmd.com/read/28753430/defining-a-cancer-dependency-map
#11
Aviad Tsherniak, Francisca Vazquez, Phil G Montgomery, Barbara A Weir, Gregory Kryukov, Glenn S Cowley, Stanley Gill, William F Harrington, Sasha Pantel, John M Krill-Burger, Robin M Meyers, Levi Ali, Amy Goodale, Yenarae Lee, Guozhi Jiang, Jessica Hsiao, William F J Gerath, Sara Howell, Erin Merkel, Mahmoud Ghandi, Levi A Garraway, David E Root, Todd R Golub, Jesse S Boehm, William C Hahn
Most human epithelial tumors harbor numerous alterations, making it difficult to predict which genes are required for tumor survival. To systematically identify cancer dependencies, we analyzed 501 genome-scale loss-of-function screens performed in diverse human cancer cell lines. We developed DEMETER, an analytical framework that segregates on- from off-target effects of RNAi. 769 genes were differentially required in subsets of these cell lines at a threshold of six SDs from the mean. We found predictive models for 426 dependencies (55%) by nonlinear regression modeling considering 66,646 molecular features...
July 27, 2017: Cell
https://www.readbyqxmd.com/read/28750090/target-specificity-in-vivo-pharmacokinetics-and-efficacy-of-the-putative-stat3-inhibitor-ly5-in-osteosarcoma-ewing-s-sarcoma-and-rhabdomyosarcoma
#12
Peter Y Yu, Heather L Gardner, Ryan Roberts, Hakan Cam, Seethalakshmi Hariharan, Ling Ren, Amy K LeBlanc, Hui Xiao, Jiayuh Lin, Denis C Guttridge, Xiaokui Mo, Chad E Bennett, Christopher C Coss, Yonghua Ling, Mitch A Phelps, Peter Houghton, Cheryl A London
BACKGROUND: STAT3 is a transcription factor involved in cytokine and receptor kinase signal transduction that is aberrantly activated in a variety of sarcomas, promoting metastasis and chemotherapy resistance. The purpose of this work was to develop and test a novel putative STAT3 inhibitor, LY5. METHODS AND FINDINGS: An in silico fragment-based drug design strategy was used to create LY5, a small molecule inhibitor that blocks the STAT3 SH2 domain phosphotyrosine binding site, inhibiting homodimerization...
2017: PloS One
https://www.readbyqxmd.com/read/28744809/vimentin-is-a-crucial-target-for-anti-metastasis-therapy-of-nasopharyngeal-carcinoma
#13
Wei Wang, Mei Yi, Renya Zhang, Junjun Li, Shengnan Chen, Jing Cai, Zhaoyang Zeng, Xiaoling Li, Wei Xiong, Li Wang, Guiyuan Li, Bo Xiang
Nasopharyngeal carcinoma (NPC) is a unique subtype of head and neck cancer, with tendency to spread to regional lymph nodes and distant organs at early stage. Vimentin, a major cytoskeletal protein constituent of the intermediate filament, plays a critical role in the epithelial-mesenchymal transition. Overexpression of vimentin is considered to be a critical prerequisite for metastasis in numerous human cancers. Therefore, targeting vimentin for cancer therapy has gained a lot of interest. In the present study, we detected vimentin expression in NPC tissues and found that overexpression of vimentin is associated with poor prognosis of NPC patients...
July 25, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28741490/in-vivo-rnai-screening-for-pancreatic-cancer-drivers-piloting-the-wdr5-myc-axis
#14
Günter Schneider, Dieter Saur
Pancreatic ductal adenocarcinoma (PDAC) represents a major global health problem that causes over 200000 deaths each year worldwide. The disease is highly resistant to cytotoxic and targeted therapies and the average survival is less than 12 months. This situation prompted Alessandro Carugo and Giulio Draetta to develop a novel genetic mouse system, termed Patient-Based In Vivo Lethality to Optimize Treatment (PILOT), to perform functional RNAi-based in vivo screens to uncover and target PDAC drivers. In a forward genetic screen focused on epigenetic modifiers, a WDR5-Myc axis that regulates the DNA replication checkpoint was identified and exploited in vivo for therapeutic intervention...
August 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28734980/histone-demethylase-phf8-regulates-hypoxia-signaling-through-hif1%C3%AE-and-h3k4me3
#15
Peterson Kariuki Maina, Peng Shao, Xiongfei Jia, Qi Liu, Shaikamjad Umesalma, Maximo Marin, Donald Long, Samantha Concepción-Román, Hank Heng Qi
Hypoxia through transcription factor HIF1α plays a critical role in cancer development. In prostate cancer, HIF1α interplays with androgen receptor (AR) to contribute to the progression of this disease to its lethal form-castration-resistant prostate cancer (CRPC). Hypoxia upregulates several epigenetic factors including histone demethylase KDM3A which is a critical co-factor of HIF1α. However, how histone demethylases regulate hypoxia signaling is not fully understood. Here, we report that histone demethylase PHF8 plays an essential role in hypoxia signaling...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28730479/analysis-of-drug-resistance-using-kinome-wide-functional-screens
#16
Katherine R Singleton, Keith T Earley, Lynn E Heasley
The clinical success of tyrosine kinase inhibitors specific for BCR-ABL-, EGFR-, ALK-, and ROS1-driven cancers continues to spur the quest to match specific oncogene-defined tumor types with an appropriate molecularly targeted therapy. Unfortunately, responses to these agents are not durable with intrinsic or acquired resistance limiting benefit. Additionally, efforts to identify the appropriate targets of new drugs have focused on nonfunctional assays such as large-scale sequencing for somatic mutations or analysis of gene copy number...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730444/oxime-ether-lipids-as-transfection-agents-assembly-and-complexation-with-sirna
#17
Anu Puri, Serena Zampino, Mathias Viard, Bruce A Shapiro
RNAi-based therapeutic approaches to combat cancer and other diseases are currently an area of great interest. However, practical applications of this approach rely on optimal tools to carry and deliver siRNA to the desired site. Oxime ether lipids (OELs) are a class of molecules among other various carriers being examined for siRNA delivery. OELs, relatively new candidates, belong to a class of non-glycerol based lipids and have begun to claim their place as an siRNA delivery carrier in the field of RNAi therapy...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730440/cellular-delivery-of-sirnas-using-bolaamphiphiles
#18
Kshitij Gupta
Discovery of RNA interference (RNAi) has opened up a new arena of therapeutic intervention for the treatment of cancerous as well as noncancerous diseases. The RNAi pathway utilizes RNAi inducers such as small interfering RNAs (siRNAs) to target and silence disease causing genes. However, efficient delivery of siRNAs for eliciting efficacious RNAi has remained a daunting challenge. Nonviral vectors such as lipids have shown great promise in delivering siRNAs. Recently, a novel class of cationic lipid molecules "bolaamphiphile lipids" or "bola lipids" has been shown to deliver siRNAs to cause effective gene silencing in cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28724889/aptamer-mediated-survivin-rnai-enables-5-fluorouracil-to-eliminate-colorectal-cancer-stem-cells
#19
Hadi AlShamaileh, Tao Wang, Dongxi Xiang, Wang Yin, Phuong Ha-Lien Tran, Roberto A Barrero, Pei-Zhuo Zhang, Yong Li, Lingxue Kong, Ke Liu, Shu-Feng Zhou, Yingchun Hou, Sarah Shigdar, Wei Duan
The development of chemoresistance and inability in elimination of cancer stem cells are among the key limitations of cancer chemotherapy. Novel molecular therapeutic strategies able to overcome such limitations are urgently needed for future effective management of cancer. In this report, we show that EpCAM-aptamer-guided survivin RNAi effectively downregulated survivin both in colorectal cancer cells in vitro and in a mouse xenograft model for colorectal cancer. When combined with the conventional chemotherapeutic agents, the aptamer-guided survivin RNAi was able to enhance the sensitivity towards 5-FU or oxaliplatin in colorectal cancer stem cells, increase apoptosis, inhibit tumour growth and improve the overall survival of mice bearing xenograft colorectal cancer...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724888/crosscheck-an-open-source-web-tool-for-high-throughput-screen-data-analysis
#20
Jamil Najafov, Ayaz Najafov
Modern high-throughput screening methods allow researchers to generate large datasets that potentially contain important biological information. However, oftentimes, picking relevant hits from such screens and generating testable hypotheses requires training in bioinformatics and the skills to efficiently perform database mining. There are currently no tools available to general public that allow users to cross-reference their screen datasets with published screen datasets. To this end, we developed CrossCheck, an online platform for high-throughput screen data analysis...
July 19, 2017: Scientific Reports
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