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https://www.readbyqxmd.com/read/28088786/ezh2-inhibition-suppresses-endometrial-cancer-progression-via-mir-361-twist-axis
#1
Kei Ihira, Peixin Dong, Ying Xiong, Hidemichi Watari, Yosuke Konno, Sharon Jb Hanley, Masayuki Noguchi, Noriyuki Hirata, Futoshi Suizu, Takahiro Yamada, Masataka Kudo, Noriaki Sakuragi
EZH2 inhibition and reactivation of tumor suppressor microRNAs (miRNAs) represent attractive anti-cancer therapeutic strategies. We found that EZH2-suppressed let 7b and miR-361, two likely tumor suppressors, inhibited endometrial cancer (EC) cell proliferation and invasion, and abrogated cancer stem cell-like properties. In EC cells, EZH2 induced and functioned together with YY1 to epigenetically suppress miR-361, which upregulated Twist, a direct target of miR-361. Treating EC cells with GSK343, a specific EZH2 inhibitor, mimicked the effects of siRNA-mediated EZH2 knockdown, upregulating miR-361 and downregulating Twist expression...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088781/mir-30c-5p-ameliorates-hepatic-steatosis-in-leptin-receptor-deficient-db-db-mice-via-down-regulating-fasn
#2
Jiahui Fan, Huaping Li, Xiang Nie, Zhongwei Yin, Yanru Zhao, Chen Chen, Dao Wen Wang
Approximately 15-40% of the general adult population suffers from non-alcoholic fatty liver disease (NAFLD) worldwide. However, no drug is currently licensed for its treatment. In this study, we observed a significant reduction of miR-30c-5p in the liver of leptin receptor-deficient (db/db) mice. Remarkably, recombinant adeno-associated virus (rAAV)-mediated delivery of miR-30c-5p was sufficient to attenuate triglyceride accumulation and hepatic steatosis in db/db mice. Through computational prediction, KEGG analysis and Ago2 co-immunoprecipitation, we identified that miR-30c-5p directly targeted fatty acid synthase, a key enzyme in fatty acid biosynthesis...
January 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088735/long-non-coding-rna-ccat1-promotes-human-retinoblastoma-so-rb50-and-y79-cells-through-negative-regulation-of-mir-218-5p
#3
Hongxu Zhang, Jianguang Zhong, Zhenyu Bian, Xiang Fang, You Peng, Yongping Hu
OBJECTIVE: To investigate the regulatory role and potential mechanism of long non-coding RNAs (lncRNA) in human retinoblastoma (RB). METHODS: The lncRNA profile in RB tissues were analyzed by microarray and quantitative reverse transcription PCR (qRT-PCR). One of the identified lncRNAs (LncRNA CCAT1) was selected for further experiments. SO-RB50 and Y79 cells were transfected with negative control, siRNA targeting lncRNA CCAT1 (si-CCAT1) and si-CCAT1+miR218-5p inhibitor, respectively...
January 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28088614/ccaat-enhancer-binding-protein-%C3%AE-promotes-pathogenesis-of-eae
#4
Michelle R Simpson-Abelson, Gerard Hernandez-Mir, Erin E Childs, J Agustin Cruz, Amanda C Poholek, Ansuman Chattopadhyay, Sarah L Gaffen, Mandy J McGeachy
The CCAAT/Enhancer Binding Protein β (C/EBPβ) transcription factor is activated by multiple inflammatory stimuli, including IL-17 and LPS, and C/EBPβ itself regulates numerous genes involved in inflammation. However, the role of C/EBPβ in driving autoimmunity is not well understood. Here, we demonstrate that Cebpb(-/-) mice are resistant to EAE. Cebpb(-/-) mice exhibited reduced lymphocyte and APC infiltration into CNS following EAE induction. Furthermore, MOG-induced Th17 cytokine production was impaired in draining LN, indicating defects in Th17 cell priming...
January 12, 2017: Cytokine
https://www.readbyqxmd.com/read/28088579/the-microrna-449-family-inhibits-tgf-%C3%AE-mediated-liver-cancer-cell-migration-by-targeting-sox4
#5
Maria Sandbothe, Reena Buurman, Nicole Reich, Luisa Greiwe, Beate Vajen, Engin Gürlevik, Vera Schäffer, Marlies Eilers, Florian Kühnel, Alejandro Vaquero, Thomas Longerich, Stephanie Roessler, Peter Schirmacher, Michael P Manns, Thomas Illig, Brigitte Schlegelberger, Britta Skawran
BACKGROUND & AIMS: Modulation of microRNA expression is considered for treatment of hepatocellular carcinoma (HCC). Therefore, we characterized the epigenetically regulated microRNA-449 family (miR-449a, miR-449b, miR-449c) with regards to its functional effects and target genes in HCC. METHODS: After transfection of miR-449a, miR-449b, and/or miR-449c, tumor-relevant functional effects were analyzed using in vitro assays and a xenograft mouse model. Binding specificities, target genes, and regulated pathways of each microRNA were identified by microarray analyses...
January 11, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28088556/regulation-of-docetaxel-sensitivity-in-prostate-cancer-cells-by-hsa-mir-125a-3p-via-modulation-of-mta1-signaling
#6
Jian-Zhou Liu, Feng-Yan Yin, Chang-You Yan, Hui Wang, Xiao-Hui Luo
OBJECTIVE: To identify the potential down-stream targets of hsa-miR-125a-3p, a mature form of miR-125a, during the pathogenesis of chemoresistance in prostate cancer (PCa). METHODS: Expression levels of hsa-miR-125a-3p was assessed in chemoresistant PCa tissues and experimentally-established chemoresistant cells using quantitative RT-PCR (qRT-PCR). The effect of hsa-miR-125a-3p knockdown or hsa-miR-125a-3p overexpression on the Dox-induced cell death was evaluated using apoptosis ELISA in chemosensitive PC-3 cells or in chemoresistant PC-3 cells (PC-3R)...
January 11, 2017: Urology
https://www.readbyqxmd.com/read/28088554/mir-99a-suppresses-proliferation-migration-invasion-and-induces-g1-phase-cell-cycle-arrest-via-targeting-igf-1r-pathway-in-renal-cell-carcinoma-786-0-and-os-rc-2-cells
#7
Bo Hao, Li Cui, Yi Gu, Bo Zhang, Min Wang, Hua Zhou, Renfang Xu, XiaoZhou He
OBJECTIVE: To explore the potential mechanism of microRNA-99a (miR-99a) and IGF-1R (insulin-like growth factor 1 receptor) accounting for RCC. MATERIALS AND METHODS: The RCC 786-O and OS-RC-2 cells were transfected with miR-99a mimics or small interfering RNA (siRNA) that silence the IGF-1R (IGF-1R-siRNA) to upregulate the expression of miR-99a and to downregulate the expression of IGF-1R. Real-time PCR and western-blot were used to detect the expression of proteins...
January 11, 2017: Urology
https://www.readbyqxmd.com/read/28088550/novel-involvement-of-mir-522-3p-in-high-mobility-group-box-1-induced-prostaglandin-reductase-1-expression-and-reduction-of-phagocytosis
#8
Gyeoung-Jin Kang, Hye-Ja Lee, Hyun Jung Byun, Eun Ji Kim, Hyun Ji Kim, Mi Kyung Park, Chang-Hoon Lee
Resolution of inflammation is important for physiological homeostasis. Chronic inflammatory diseases may be caused by abnormal resolution of inflammation. However, what causes a failure of inflammatory resolution is unclear. Here we investigated the involvement of high mobility group box 1 (HMGB1) protein in the control of inflammatory resolution as a 'anti-resolution factor'. We first confirmed the increased expression of HMGB1 and prostaglandin reductase 1 (PTGR1) in inflammatory conditions and HMGB1-mediated regulation of the expression of PTGR1...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28088526/subcutaneous-immunization-with-streptococcus-pneumoniae-gapdh-confers-effective-protection-in-mice-via-tlr2-and-tlr4
#9
Xiaoyu Sun, Jichao Wang, Jie Zhou, Hong Wang, Xiaofang Wang, Jingwen Wu, Yujuan He, Yibing Yin, Xuemei Zhang, Wenchun Xu
The surface localized Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of Streptococcus pneumoniae is best known as housekeeping protein. Currently, GAPDH has been recognized as moonlighting protein and virulent factor. Therefore, we investigate whether GAPDH can act as a suitable vaccine candidate protein to prevent pneumococcal infection. In this study, mice received subcutaneous vaccination with recombinant GAPDH followed by challenge with D39 and 19F showing higher survival rate and lower bacterial loads in nasal washes and lung homogenates than control...
January 12, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28088520/palmitic-acid-increases-invasiveness-of-pancreatic-cancer-cells-aspc-1-through-tlr4-ros-nf-%C3%AE%C2%BAb-mmp-9-signaling-pathway
#10
Makena J Binker-Cosen, Daniel Richards, Brenda Oliver, Herbert Y Gaisano, Marcelo G Binker, Laura I Cosen-Binker
Pancreatic cancer (PC) is an aggressive malady with proclivity for early metastasis. Overexpression of toll-like receptor 4 (TLR4) in pancreatic ductal adenocarcinoma, the most common type of pancreatic malignancy, correlates to tumor size, lymph node involvement, venous invasion and pathological stage. Lipopolysaccharides (LPS) are natural TLR4 ligands that have been shown to increase the invasive ability of PC cells. However, rapid inactivation of circulating LPS and low systemic absorption of inhaled LPS from the bronchoalveolar compartment make other agonists such as saturated fatty acids more suitable to be considered for TLR4-related cell invasiveness...
January 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28088503/evidence-for-splice-transcript-variants-of-tmem165-a-gene-involved-in-cdg
#11
Marie-Ange Krzewinski-Recchi, Sven Potelle, Anne Marie-Mir, Dorothée Vicogne, Eudoxie Dulary, Sandrine Duvet, Willy Morelle, Geoffroy de Bettignies, François Foulquier
BACKGROUND: Defects in TMEM165 gene cause a type-II Congenital Disorder of Glycosylation affecting Golgi glycosylation processes. TMEM165 patients exhibit psychomotor retardation, important osteoporosis, scoliosis, irregular epiphyses and thin bone cortex. Human TMEM165 protein is highly conserved in evolution and belongs to the family of UPF0016 membrane proteins which could be an unique group of Ca(2+)/H(+) antiporters regulating Ca(2+) and pH homeostasis and mainly localized in the Golgi apparatus...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28088407/far-off-and-close-up-dry-matter-intake-modulate-indicators-of-immunometabolic-adaptations-to-lactation-in-subcutaneous-adipose-tissue-of-pasture-based-transition-dairy-cows
#12
M Vailati-Riboni, G Farina, F Batistel, A Heiser, M D Mitchell, M A Crookenden, C G Walker, J K Kay, S Meier, J R Roche, J J Loor
The common practice of increasing dietary energy density during the close-up dry period (last ∼3 wk prepartum) has been recently associated with a higher incidence of metabolic disorders after calving. Despite these reports, over-feeding of metabolizable energy (ME) during the far-off, nonlactating period is a common management policy aimed at achieving optimum calving body condition score (BCS) in pasture-based systems, as cows are generally thinner than total mixed ration cows at the end of lactation. Our hypothesis was that both far-off and close-up overfeeding influence the peripartum adipose tissue changes associated with energy balance and inflammatory state...
January 11, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28088404/variation-in-fat-globule-size-in-bovine-milk-and-its-prediction-using-mid-infrared-spectroscopy
#13
A Fleming, F S Schenkel, J Chen, F Malchiodi, R A Ali, B Mallard, M Sargolzaei, M Corredig, F Miglior
The objectives of this study were to investigate the sources of variation in milk fat globule (MFG) size in bovine milk and its prediction using mid-infrared (MIR) spectroscopy. Mean MFG size was measured in 2,076 milk samples from 399 Ayrshire, Brown Swiss, Holstein, and Jersey cows, and expressed as volume moment mean (D[4,3]) and surface moment mean (D[3,2]). The mid-infrared spectra of the samples and milk performance data were also recorded during routine milk recording and testing. The effects of breed, herd nested within breed, days in milk, season, milking period, age at calving, parity, and individual animal on the variation observed in MFG size were investigated...
January 11, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28088385/flavonoid-derivative-fla-cn-inhibited-adipocyte-differentiation-via-activating-ampk-and-up-regulating-microrna-27-in-3t3-l1-cells
#14
Chun-Chun Gan, Tian-Wen Ni, Yang Yu, Nan Qin, Ying Chen, Mei-Na Jin, Hong-Quan Duan
Fla-CN (3-O-[(E)-4-(4-cyanophenyl)-2-oxobut-3-en-1-yl] kaempferol) is a semi-synthesized flavonoid derivative of tiliroside which exhibited anti-diabetic effect in vivo. Our previous study revealed the role of Fla-CN in anti-obesity and anti-diabetes in vivo, but the underlying mechanism remained to be addressed. The present study aimed to investigate the mechanism of anti-adipogenesis in vitro. Fla-CN markedly inhibited intracellular lipid accumulation in a dose-dependent manner, and the inhibitory effect was mainly limited to the early stage of adipocyte differentiation in vitro...
January 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28088076/in%C3%A2-vivo-visualization-of-endogenous-mir-21-using-hyaluronic-acid-coated-graphene-oxide-for-targeted-cancer-therapy
#15
Do Won Hwang, Han Young Kim, Fangyuan Li, Ji Yong Park, Dohyun Kim, Jae Hyung Park, Hwa Seung Han, Jung Woo Byun, Yun-Sang Lee, Jae Min Jeong, Kookheon Char, Dong Soo Lee
Oncogene-targeted nucleic acid therapy has been spotlighted as a new paradigm for cancer therapeutics. However, in vivo delivery issues and uncertainty of therapeutic antisense drug reactions remain critical hurdles for a successful targeted cancer therapy. In this study, we developed a fluorescence-switchable theranostic nanoplatform using hyaluronic acid (HA)-conjugated graphene oxide (GO), which is capable of both sensing oncogenic miR-21 and inhibiting its tumorigenicity simultaneously. Cy3-labeled antisense miR-21 peptide nucleic acid (PNA) probes loaded onto HA-GO (HGP21) specifically targeted CD44-positive MBA-MB231 cells and showed fluorescence recovery by interacting with endogenous miR-21 in the cytoplasm of the MBA-MB231 cells...
December 31, 2016: Biomaterials
https://www.readbyqxmd.com/read/28087860/retraction-note-triptolide-contributes-to-decrease-in-tlr4-expression-by-upregulating-mir-224-3p-to-inhibit-the-inflammatory-reaction-in-diabetic-nephropathy
#16
Bei Sun, Shaolan Hu, Yongmei Li, Endong Zhu, Li Li, Fei Han, Chun-Jun Li, Liming Chen
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December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/28087411/aspirin-prevents-tnf-%C3%AE-induced-endothelial-cell-dysfunction-by-regulating-the-nf-%C3%AE%C2%BAb-dependent-mir-155-enos-pathway-role-of-a-mir-155-enos-axis-in-preeclampsia
#17
Joohwan Kim, Kyu-Sun Lee, Ji-Hee Kim, Dong-Keon Lee, Minsik Park, Seunghwan Choi, Wonjin Park, Suji Kim, Yoon Kyoung Choi, Jong Yun Hwang, Jongseon Choe, Moo-Ho Won, Dooil Jeoung, Hansoo Lee, Sungwoo Ryoo, Kwon-Soo Ha, Young-Guen Kwon, Young-Myeong Kim
Preeclampsia is an inflammatory disease with endothelial cell dysfunction that occurs via decreased endothelial nitric oxide synthase/nitric oxide (eNOS/NO) activity. Aspirin reduces the incidence of hypertensive pregnancy complications. However, the underlying mechanism has not been clearly explained. Here, we found that tumor necrosis factor (TNF)-α, microRNA (miR)-155, and eNOS levels as well as endothelial redox phenotype were differentially regulated in preeclamptic patients, implying the involvement of TNF-α- and redox signal-mediated miR-155 biogenesis and eNOS downregulation in the pathogenesis of preeclampsia...
January 10, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28087162/mir-24-inhibition-increases-menin-expression-and-decreases-cholangiocarcinoma-proliferation
#18
Laurent Ehrlich, Chad Hall, Julie Venter, David Dostal, Francesca Bernuzzi, Pietro Invernizzi, Fanyin Meng, Jerome P Trzeciakowski, Tianhao Zhou, Holly Standeford, Gianfranco Alpini, Terry C Lairmore, Shannon Glaser
Menin (MEN1) is a tumor-suppressor protein in neuroendocrine tissue. Because cholangiocytes can take on a neuroendocrine phenotype, we tested the novel hypothesis that menin regulates cholangiocarcinoma proliferation. Menin and miR-24 expression levels were measured in the following intrahepatic and extrahepatic cholangiocarcinoma (CCA) cell lines, Mz-ChA-1, TFK-1, SG231, CCLP, HuCCT-1, and HuH-28, as well as the nonmalignant human intrahepatic biliary line, H69. miR-24 miRNA and menin protein levels were manipulated in vitro in Mz-ChA-1 cell lines...
January 10, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28087069/safety-tolerability-and-antiviral-effect-of-rg-101-in-patients-with-chronic-hepatitis-c-a-phase-1b-double-blind-randomised-controlled-trial
#19
Meike H van der Ree, J Marleen de Vree, Femke Stelma, Sophie Willemse, Marc van der Valk, Svend Rietdijk, Richard Molenkamp, Janke Schinkel, Ad C van Nuenen, Ulrich Beuers, Salah Hadi, Marten Harbers, Eva van der Veer, Kai Liu, John Grundy, Amy K Patick, Adam Pavlicek, Jacqueline Blem, Michael Huang, Paul Grint, Steven Neben, Neil W Gibson, Neeltje A Kootstra, Hendrik W Reesink
BACKGROUND: miR-122 is an important host factor for hepatitis C virus (HCV) replication. The aim of this study was to assess the safety and tolerability, pharmacokinetics, and antiviral effect of a single dose of RG-101, a hepatocyte targeted N-acetylgalactosamine conjugated oligonucleotide that antagonises miR-122, in patients with chronic HCV infection with various genotypes. METHODS: In this randomised, double-blind, placebo-controlled, multicentre, phase 1B study, patients were randomly assigned to RG-101 or placebo (7:1)...
January 10, 2017: Lancet
https://www.readbyqxmd.com/read/28086946/mir-1307-promotes-ovarian-cancer-cell-chemoresistance-by-targeting-the-ing5-expression
#20
Wen-Ting Chen, Yu-Jia Yang, Zhen-Dong Zhang, Qiang An, Na Li, Wei Liu, Bing Yang
BACKGROUND: We aimed to investigate the function of miR-1307 in chemoresistance and to explore its chemoresistance mechanism in ovarian cancer. METHODS: IC50 determination was used to test the chemoresistance profling in ovarian cancer cells. QRT-PCR or western blot was used to validate the expression level of miR-1307 and candidate gene or protein. Colony formation assay and FITC-labeled enhanced Annexin V immunofluorescence were used to compare cell proliferation and apoptosis ability, respectively...
January 11, 2017: Journal of Ovarian Research
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