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In vivo gene silencing

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https://www.readbyqxmd.com/read/28073943/kdm4b-jmjd2b-is-a-p53-target-gene-that-modulates-the-amplitude-of-p53-response-after-dna-damage
#1
Laura Castellini, Eui Jung Moon, Olga V Razorenova, Adam J Krieg, Rie von Eyben, Amato J Giaccia
The p53 tumor suppressor protein plays a critical role in orchestrating the genomic response to various stress signals by acting as a master transcriptional regulator. Differential gene activity is controlled by transcription factors but also dependent on the underlying chromatin structure, especially on covalent histone modifications. After screening different histone lysine methyltransferases and demethylases, we identified JMJD2B/KDM4B as a p53-inducible gene in response to DNA damage. p53 directly regulates JMJD2B gene expression by binding to a canonical p53-consensus motif in the JMJD2B promoter...
January 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28073915/ube2e1-ubch6-is-a-critical-in-vivo-e2-for-the-prc1-catalyzed-ubiquitination-of-h2a-at-k119
#2
Keith Wheaton, Feroz Sarkari, Beena Stanly Johns, Hossein Davarinejad, Olga Egorova, Lilia Kaustov, Brian Raught, Vivian Saridakis, Yi Sheng
UbE2E1/UbcH6 is an E2 ubiquitin conjugating enzyme that is regulated by USP7. We identified UbE2E1 as a novel component of Polycomb Repressive Complex 1 (PRC1), the E3 ligase complex responsible for histone H2A ubiquitination and gene silencing. We demonstrate that UbE2E1 is critical for the mono-ubiquitination of H2A at residue K119 (uH2AK119) through its association with the PRC1 complex. UbE2E1 interacts with PRC1 subunits including Ring1A and Ring1B. Overexpression of UbE2E1 results in increased levels of uH2AK119 whereas overexpression of catalytically inactive UbE2E1C131A or UbE2E1 knockdown results in decreased levels of uH2AK119...
January 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28073170/loss-of-hsef-promotes-metastasis-through-up-regulation-of-emt-in-prostate-cancer
#3
S Hori, K Wadhwa, V Pisupati, V Zecchini, A Ramos-Montoya, A Y Warren, D E Neal, V J Gnanapragasam
We have previously reported that the negative regulator Similar Expression to FGF (hSef) is down-regulated in prostate cancer and its loss is associated with clinical metastasis. Here, we explored the mechanistic basis of this finding. We first confirmed our clinical observation by testing hSef manipulation in an in vivo metastasis model. hSef stable expressing cells (PC3M-hSef) or empty vector controls (PC3M-EV) were injected subcutaneously into the lateral thoracic walls of NOD-SCID gamma mice and lungs were harvested at autopsy...
January 10, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28070757/rnai-induced-electrophysiological-and-behavioral-changes-reveal-two-pheromone-binding-proteins-of-helicoverpa-armigera-involved-in-the-perception-of-the-main-sex-pheromone-component-z11-16-ald
#4
Kun Dong, Liang Sun, Jing-Tao Liu, Shao-Hua Gu, Jing-Jiang Zhou, Ruo-Nan Yang, Khalid Hussain Dhiloo, Xi-Wu Gao, Yu-Yuan Guo, Yong-Jun Zhang
Pheromone binding proteins (PBPs) are thought to play key roles in insect sex pheromone recognition; however, there is little in vivo evidence to support this viewpoint in comparison to abundant biochemical data in vitro. In the present study, two noctuid PBP genes HarmPBP1 and HarmPBP2 of the serious agricultural pest, Helicoverpa armigera were selected to be knocked down by RNA interference, and then the changes in electrophysiological and behavioral responses of male mutants to their major sex pheromone component (Z)-11-hexadecenal (Z11-16:Ald) were recorded...
January 9, 2017: Journal of Chemical Ecology
https://www.readbyqxmd.com/read/28068223/hepatocyte-taz-wwtr1-promotes-inflammation-and-fibrosis-in-nonalcoholic-steatohepatitis
#5
Xiaobo Wang, Ze Zheng, Jorge Matias Caviglia, Kathleen E Corey, Tina M Herfel, Bishuang Cai, Ricard Masia, Raymond T Chung, Jay H Lefkowitch, Robert F Schwabe, Ira Tabas
Nonalcoholic steatohepatitis (NASH) is a leading cause of liver disease worldwide. However, the molecular basis of how benign steatosis progresses to NASH is incompletely understood, which has limited the identification of therapeutic targets. Here we show that the transcription regulator TAZ (WWTR1) is markedly higher in hepatocytes in human and murine NASH liver than in normal or steatotic liver. Most importantly, silencing of hepatocyte TAZ in murine models of NASH prevented or reversed hepatic inflammation, hepatocyte death, and fibrosis, but not steatosis...
December 13, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28067782/rna-interference-for-mosquito-and-mosquito-borne-disease-control
#6
REVIEW
Paul M Airs, Lyric C Bartholomay
RNA interference (RNAi) is a powerful tool to silence endogenous mosquito and mosquito-borne pathogen genes in vivo. As the number of studies utilizing RNAi in basic research grows, so too does the arsenal of physiological targets that can be developed into products that interrupt mosquito life cycles and behaviors and, thereby, relieve the burden of mosquitoes on human health and well-being. As this technology becomes more viable for use in beneficial and pest insect management in agricultural settings, it is exciting to consider its role in public health entomology...
January 5, 2017: Insects
https://www.readbyqxmd.com/read/28061796/glucose-transporter-4-promotes-head-and-neck-squamous-cell-carcinoma-metastasis-through-the-trim24-ddx58-axis
#7
Yu-Chan Chang, Li-Hsing Chi, Wei-Ming Chang, Chia-Yi Su, Yuang-Feng Lin, Chi-Long Chen, Ming-Huang Chen, Peter Mu-Hsin Chang, Alex T H Wu, Michael Hsiao
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) represents a unique and major health concern worldwide. Significant increases in glucose uptake and aerobic glycolysis have been observed in HNSCC cells. Glucose transporters (GLUTs) represent a major hub in the glycolysis pathway, with GLUT4 having the highest glucose affinity. However, GLUT4's role in HNSCC has not been fully appreciated. METHODS: An in silico analysis was performed in HNSCC cohorts to identify the most significant glucose transporter associated with HNSCC patient prognosis...
January 7, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28059830/2-deoxy-d-glucose-suppresses-the-migration-and-reverses-the-drug-resistance-of-colon-cancer-cells-through-adam-expression-regulation
#8
Ga B Park, Yoon H Chung, Daejin Kim
Cancer cell resistance to chemotherapy is associated with a poor prognosis. The compound 2-deoxy-D-glucose (2-DG) enhances the effect of chemotherapy against cancer cells lines in vitro and in vivo. However, its effect on the epithelial to mesenchymal transition (EMT) in drug-resistant cancer cells has not been fully elucidated. In this study, we investigated whether treatment of 5-fluorouracil or oxaliplatin-resistant colorectal cancer (CRC) cells with 2-DG suppressed their migratory activity and enhanced their susceptibility to chemotherapy...
January 2, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28057611/wnt-5a-regulates-tgf%C3%AE-related-activities-in-liver-fibrosis
#9
Leonie Beljaars, Sara Daliri, Christa Dijkhuizen, Klaas Poelstra, Reinoud Gosens
WNT-5A is a secreted growth factor that belongs to the non-canonical members of the Wingless-related MMTV-integration family. Previous studies pointed to a connection between WNT-5A and the fibrogenic factor TGF-β warranting further studies into the functional role of WNT-5A in liver fibrosis. Therefore, we studied WNT-5A expressions in mouse and human fibrotic livers and examined the relation between WNT-5A and various fibrosis-associated growth factors, cytokines and extracellular matrix proteins. WNT-5A gene and protein expressions were significantly increased in fibrotic mouse and human livers compared to healthy...
January 5, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28056547/analysis-of-hypoxia-induced-noncoding-rnas-reveals-metastasis-associated-lung-adenocarcinoma-transcript-1-as-an-important-regulator-of-vascular-smooth-muscle-cell-proliferation
#10
Matthias Brock, Claudio Schuoler, Caroline Leuenberger, Carlo Bühlmann, Thomas J Haider, Johannes Vogel, Silvia Ulrich, Max Gassmann, Malcolm Kohler, Lars C Huber
Vascular remodeling, a pathogenic hallmark in pulmonary hypertension, is mainly driven by a dysbalance between proliferation and apoptosis of human pulmonary artery smooth muscle cells. It has previously been shown that microRNAs are involved in the pathogenesis of pulmonary hypertension. However, the role of long noncoding RNAs has not been evaluated. long noncoding RNA expression was quantified in human pulmonary artery smooth muscle cells using PCR arrays and quantitative PCR. Knockdown of genes was performed by transfection of siRNA or GapmeR...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28056393/increased-expression-of-negative-regulators-of-cytokine-signaling-during-chronic-hiv-disease-cause-functionally-exhausted-state-of-dendritic-cells
#11
Meenakshi Sachdeva, Aman Sharma, Sunil K Arora
Mechanisms of functional impairment of dendritic cells (DCs) during chronic HIV-1 infection are not well understood. In order to understand this phenomenon, we aimed to study the expression of negative regulators of cytokine signaling and correlate with DC exhaustion during chronic HIV-1 disease. Monocyte-derived DCs (mo-DCs) from 27 HIV-1 infected patients (CD4+ T-cell counts: 429±44 cells/μL, plasma viral load: Log103.9±1.0copies/ml) and 19 healthy controls (HCs) were stimulated ex vivo with TLR4 agonist, lipopolysaccharide (LPS) for 2days to evaluate their functional fitness...
January 2, 2017: Cytokine
https://www.readbyqxmd.com/read/28056049/asc-induces-apoptosis-via-activation-of-caspase-9-by-enhancing-gap-junction-mediated-intercellular-communication
#12
Masato Kitazawa, Shigeaki Hida, Chifumi Fujii, Shun'ichiro Taniguchi, Kensuke Ito, Tomio Matsumura, Nagisa Okada, Takashi Sakaizawa, Akira Kobayashi, Michiko Takeoka, Shin-Ichi Miyagawa
ASC (apoptosis-associated speck-like protein containing a CARD) is a key adaptor molecule of inflammasomes that mediates inflammatory and apoptotic signals. Aberrant methylation-induced silencing of ASC has been observed in a variety of cancer cells, thus implicating ASC in tumor suppression, although this role remains incompletely defined especially in the context of closely neighboring cell proliferation. As ASC has been confirmed to be silenced by abnormal methylation in HT1080 fibrosarcoma cells as well, this cell line was investigated to characterize the precise role and mechanism of ASC in tumor progression...
2017: PloS One
https://www.readbyqxmd.com/read/28054302/microrna-761-induces-aggressive-phenotypes-in-triple-negative-breast-cancer-cells-by-repressing-trim29-expression
#13
Guang-Cheng Guo, Jia-Xiang Wang, Ming-Li Han, Lian-Ping Zhang, Lin Li
PURPOSE: Despite advances that have been made in systemic chemotherapy, the prognosis of advanced triple-negative breast cancer (TNBC) patients is still poor. The identification of key factors governing TNBC development is considered imperative for the development of novel effective therapeutic approaches. Previously, it has been reported that microRNA (miR)-761 may act as either a tumor suppressor or as an oncogene in different types of cancer. Here, we aimed at assessing the biological role of this miRNA in TNBC...
January 4, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28052869/nlrp3-inflammasome-activation-contributes-to-aldosterone-induced-podocyte-injury
#14
Mi Bai, Ying Chen, Min Zhao, Yue Zhang, John Cijiang He, Songming Huang, Zhanjun Jia, Aihua Zhang
Aldosterone (Aldo) has been shown as an important contributor of podocyte injury. However, the underlying molecular mechanisms are still elusive. Recently, the pathogenic role of NLRP3 inflammasome in mediating renal tubular damage was identified while its role in podocyte injury still needs evidence. Thus the present study was undertaken to investigate the role of NLRP3 inflammasome in Aldo-induced podocyte damage. In vitro, exposure of podocytes to Aldo enhanced NLRP3, caspase-1 and IL-18 expressions in dose- and time-dependent manners, indicating an activation of NLRP3 inflammasome, which was significantly blocked by a mineralocorticoid receptor antagonist Eplerenone (EPL) or an antioxidant NAC...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28051999/foxm1-evokes-5-fluorouracil-resistance-in-colorectal-cancer-depending-on-abcc10
#15
Tao Xie, Jian Geng, Ye Wang, Liya Wang, Mengxi Huang, Jing Chen, Kai Zhang, Lijun Xue, Xiaobei Liu, Xiaobei Mao, Yanan Chen, Qian Wang, Tingting Dai, Lili Ren, Hongju Yu, Rui Wang, Longbang Chen, Cheng Chen, Xiaoyuan Chu
5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent for colorectal cancer (CRC). However, frequently occurred 5-FU resistance poses a great challenge in the clinic. Elucidating the underlying mechanisms and developing effective strategies against 5-FU resistance are highly desired. Here we identified the upregulation of FOXM1 in 5-FU nonresponsive CRC patients by gene expression profile analysis and 5-FU-resistant CRC cells by qRT-PCR assay. Silencing of FOXM1 promoted the sensitivity of CRC cells to 5-FU by enhancing cell apoptosis, while overexpression of FOXM1 conferred CRC cells with 5-FU resistance both in vitro and in vivo...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28042340/systemic-sirna-delivery-with-a-dual-ph-responsive-and-tumor-targeted-nanovector-for-inhibiting-tumor-growth-and-spontaneous-metastasis-in-orthotopic-murine-model-of-breast-carcinoma
#16
Bo Fan, Lin Kang, Liqing Chen, Ping Sun, Mingji Jin, Qiming Wang, You Han Bae, Wei Huang, Zhonggao Gao
Phenylboronic acid (PBA)-mediated tumor targeting nanovector is an attractive strategy for enhancing siRNA delivery and treatment of metastatic cancers. However, its nonspecific binding with various biological membranes containing cis-diol moieties restricts its potential application by systematic administration. Herein, we constructed a novel pH-activated "sheddable" PEG-coated nanoparticle for effective treatment of primary tumors and metastases, which was based on the conjugation of catechol group modified poly(ethylene glycol) (PEG-Cat) and PBA-terminated polyethylenimine (PEI-PBA) via the borate ester formed between PBA and Cat...
2017: Theranostics
https://www.readbyqxmd.com/read/28042317/cd54-notch1-axis-controls-tumor-initiation-and-cancer-stem-cell-functions-in-human-prostate-cancer
#17
Chong Li, Shengwu Liu, Ruping Yan, Ning Han, Kwok-Kin Wong, Lei Li
Cancer stem cells (CSCs) are considered one of the key contributors to chemoresistance and tumor recurrence. Therefore, the precise identification of reliable CSC markers and clarification of the intracellular signaling involved in CSCs remains a great challenge in fields relating to cancer biology. Here, we implemented a novel chemoresistant prostate cancer patient-derived xenograft (PDX) model in NOD/SCID mice and identified CD54 as a candidate gene among the most highly enriched gene expression profiles in prostate tumors exposed to chronic cisplatin administration...
2017: Theranostics
https://www.readbyqxmd.com/read/28039298/sublytic-c5b-9-induces-glomerular-mesangial-cell-apoptosis-through-the-cascade-pathway-of-mekk2-p38-mapk-irf-1-tradd-caspase-8-in-rat-thy-1-nephritis
#18
Ganqian Zhu, Wen Qiu, Yongting Li, Chenhui Zhao, Fengxia He, Mengya Zhou, Lulu Wang, Dan Zhao, Yanlai Lu, Jing Zhang, Yu Liu, Tianyi Yu, Yingwei Wang
The apoptosis of glomerular mesangial cells (GMCs) in the early phase of rat Thy-1 nephritis (Thy-1N), a model of human mesangioproliferative glomerulonephritis (MsPGN), is primarily triggered by sublytic C5b-9. However, the mechanism of GMC apoptosis induced by sublytic C5b-9 remains unclear. In this study, we demonstrate that expressions of TNFR1-associated death domain-containing protein (TRADD) and IFN regulatory factor-1 (IRF-1) were simultaneously upregulated in the renal tissue of Thy-1N rats (in vivo) and in GMCs under sublytic C5b-9 stimulation (in vitro)...
December 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28039207/nup358-binds-to-ago-proteins-through-its-sumo-interacting-motifs-and-promotes-the-association-of-target-mrna-with-mirisc
#19
Manas Ranjan Sahoo, Swati Gaikwad, Deepak Khuperkar, Maitreyi Ashok, Mary Helen, Santosh Kumar Yadav, Aditi Singh, Indrasen Magre, Prachi Deshmukh, Supriya Dhanvijay, Pabitra Kumar Sahoo, Yogendra Ramtirtha, Mallur Srivatsan Madhusudhan, Pananghat Gayathri, Vasudevan Seshadri, Jomon Joseph
MicroRNA (miRNA)-guided mRNA repression, mediated by the miRNA-induced silencing complex (miRISC), is an important component of post-transcriptional gene silencing. However, how miRISC identifies the target mRNA in vivo is not well understood. Here, we show that the nucleoporin Nup358 plays an important role in this process. Nup358 localizes to the nuclear pore complex and to the cytoplasmic annulate lamellae (AL), and these structures dynamically associate with two mRNP granules: processing bodies (P bodies) and stress granules (SGs)...
December 30, 2016: EMBO Reports
https://www.readbyqxmd.com/read/28038453/histone-deacetylase-inhibitor-saha-mediates-mast-cell-death-and-epigenetic-silencing-of-constitutively-active-d816v-kit-in-systemic-mastocytosis
#20
Katarina Lyberg, Hani Abdulkadir Ali, Jennine Grootens, Matilda Kjellander, Malin Tirfing, Michel Arock, Hans Hägglund, Gunnar Nilsson, Johanna Ungerstedt
Systemic mastocytosis (SM) is a clonal bone marrow disorder, where therapeutical options are limited. Over 90% of the patients carry the D816V point mutation in the KIT receptor that renders this receptor constitutively active. We assessed the sensitivity of primary mast cells (MC) and mast cell lines HMC1.2 (D816V mutated), ROSA (KIT WT) and ROSA (KIT D816V) cells to histone deacetylase inhibitor (HDACi) treatment. We found that of four HDACi, suberoyl anilide hydroxamic acid (SAHA) was the most effective in killing mutated MC...
December 25, 2016: Oncotarget
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