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https://www.readbyqxmd.com/read/28815045/tumor-derived-exosomes-induce-cd8-t-cell-suppressors
#1
Brian T Maybruck, Lukas W Pfannenstiel, Marcela Diaz-Montero, Brian R Gastman
BACKGROUND: The suppressive nature of immune cells in the tumor microenvironment plays a major role in regulating anti-tumor immune responses. Our previous work demonstrated that a soluble factor from tumor cells is able to induce a suppressor phenotype (SP) in human CD8(+) T cells typified by loss of CD27/CD28 expression and acquisition of a potent suppressor function. The present study hypothesized that the soluble mechanism that is inducing the SP in CD8(+) T cells are tumor-derived exosomes (TDEs)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28807240/role-of-exosomes-in-treatment-of-hepatocellular-carcinoma
#2
REVIEW
Demetrios Moris, Eliza W Beal, Jeffery Chakedis, Richard A Burkhart, Carl Schmidt, Mary Dillhoff, Xufeng Zhang, Stamatios Theocharis, Timothy M Pawlik
Exosomes are nanovesicles that may play a role in intercellular communication by acting as carriers of functional contents such as proteins, lipids, RNA molecules and circulating DNA from donor to recipient cells. In addition, exosomes may play a potential role in immunosurveillance and tumor pathogenesis and progression. Recently, research has increasingly focused on the role of exosomes in hepatocellular carcinoma (HCC), the most common primary liver malignancy. We herein review data on emerging experimental and clinical studies focused on the role of exosomes in the pathogenesis, diagnosis, progression and chemotherapy response of patients with HCC...
September 2017: Surgical Oncology
https://www.readbyqxmd.com/read/28806909/tumor-derived-exosomes-induce-cd8-t-cell-suppressors
#3
Brian T Maybruck, Lukas W Pfannenstiel, Marcela Diaz-Montero, Brian R Gastman
BACKGROUND: The suppressive nature of immune cells in the tumor microenvironment plays a major role in regulating anti-tumor immune responses. Our previous work demonstrated that a soluble factor from tumor cells is able to induce a suppressor phenotype (SP) in human CD8(+) T cells typified by loss of CD27/CD28 expression and acquisition of a potent suppressor function. The present study hypothesized that the soluble mechanism that is inducing the SP in CD8(+) T cells are tumor-derived exosomes (TDEs)...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28804599/circulating-exosome-microrna-associated-with-heart-failure-secondary-to-myxomatous-mitral-valve-disease-in-a-naturally-occurring-canine-model
#4
Vicky K Yang, Kerry A Loughran, Dawn M Meola, Christine M Juhr, Kristen E Thane, Airiel M Davis, Andrew M Hoffman
Myxomatous mitral valve disease (MMVD) is functionally and histologically identical to mitral valve prolapse (MVP) in humans. Currently, there are no medical treatments that can delay the progression of this valvular disease or associated cardiac remodelling. Therefore, there is a need to understand the molecular pathology associated with MMVD and MVP better, and thus identify potential therapeutic targets. Circulating exosomes contain small RNA, including miRNA, which reflect cell physiology and pathology...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28804598/a-rigorous-method-to-enrich-for-exosomes-from-brain-tissue
#5
Laura J Vella, Benjamin J Scicluna, Lesley Cheng, Emma G Bawden, Colin L Masters, Ching-Seng Ang, Nicholas Willamson, Catriona McLean, Kevin J Barnham, Andrew F Hill
Extracellular vesicles, including exosomes, are released by all cells, including those of the nervous system. Capable of delivering lipid, protein and nucleic acids to both nearby and distal cells, exosomes have been hypothesized to play a role in progression of many diseases of the nervous system. To date, most analyses on the role of these vesicles in the healthy and diseased state have relied on studying vesicles from in vitro sources, such as conditioned cell culture media, or body fluids. Here we have taken a critical approach to the enrichment and characterization of exosomes from human frontal cortex...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28801509/exosome-cofactor-hmtr4-competes-with-export-adaptor-alyref-to-ensure-balanced-nuclear-rna-pools-for-degradation-and-export
#6
Jing Fan, Bin Kuai, Guifen Wu, Xudong Wu, Binkai Chi, Lantian Wang, Ke Wang, Zhubing Shi, Heng Zhang, She Chen, Zhisong He, Siyuan Wang, Zhaocai Zhou, Guohui Li, Hong Cheng
The exosome is a key RNA machine that functions in the degradation of unwanted RNAs. Here, we found that significant fractions of precursors and mature forms of mRNAs and long noncoding RNAs are degraded by the nuclear exosome in normal human cells. Exosome-mediated degradation of these RNAs requires its cofactor hMTR4. Significantly, hMTR4 plays a key role in specifically recruiting the exosome to its targets. Furthermore, we provide several lines of evidence indicating that hMTR4 executes this role by directly competing with the mRNA export adaptor ALYREF for associating with ARS2, a component of the cap-binding complex (CBC), and this competition is critical for determining whether an RNA is degraded or exported to the cytoplasm...
August 11, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28800772/endurance-training-lowers-ribosome-density-despite-increasing-ribosome-biogenesis-markers-in-rodent-skeletal-muscle
#7
Matthew A Romero, C Brooks Mobley, Melissa A Linden, Grace Margaret-Eleanor Meers, Jeffrey S Martin, Kaelin C Young, R Scott Rector, Michael D Roberts
OBJECTIVE: The purpose of this study was to examine if: (a) high sugar/high fat Western diet (WD)-feeding affects skeletal muscle ribosome biogenesis markers in hyperphagic, diabetic-prone Otsuka Long-Evans Tokushima Fatty (OLETF) rats, and (b) 12 weeks of treadmill training rescued potential detriments that WD feeding exerted on these markers. METHODS: Eight week-old male OLETF rats were fed a low-fat control diet (O-CON, n = 10) or high/sucrose/cholesterol Western diet (WD)...
August 11, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28766848/microrna-30a-ameliorates-hepatic-fibrosis-by-inhibiting-beclin1-mediated-autophagy
#8
Jianliang Chen, Yue Yu, Shu Li, Yuting Liu, Shu Zhou, Shouji Cao, Jie Yin, Guoqiang Li
We explored the role of microRNA-30a (miR-30a) and the mechanism involved in hepatic fibrosis. MiR-30a overexpression was achieved by miR-30a mimics transfection in hepatic stellate cells (HSCs) (HSC-T6, LX-2), and miR-30a agomir (ago-miR-30a) treatment in mice. MiR-30a levels were measured using TaqMan miRNA assay system, and the localization of miR-30a was detected by fluorescence in situ hybridization (FISH). The interaction of miR-30a and Beclin1 was confirmed by dual-luciferase reporter assay. Autophagic flux was analysed using tandem mRFP-GFP-LC3 fluorescence microscopy, electron microscopy and Western blot of LC3-II/I ratio...
August 1, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28765164/selective-termination-of-lncrna-transcription-promotes-heterochromatin-silencing-and-cell-differentiation
#9
Leila Touat-Todeschini, Yuichi Shichino, Mathieu Dangin, Nicolas Thierry-Mieg, Benoit Gilquin, Edwige Hiriart, Ravi Sachidanandam, Emeline Lambert, Janine Brettschneider, Michael Reuter, Jan Kadlec, Ramesh Pillai, Akira Yamashita, Masayuki Yamamoto, André Verdel
Long non-coding RNAs (lncRNAs) regulating gene expression at the chromatin level are widespread among eukaryotes. However, their functions and the mechanisms by which they act are not fully understood. Here, we identify new fission yeast regulatory lncRNAs that are targeted, at their site of transcription, by the YTH domain of the RNA-binding protein Mmi1 and degraded by the nuclear exosome. We uncover that one of them, nam1, regulates entry into sexual differentiation. Importantly, we demonstrate that Mmi1 binding to this lncRNA not only triggers its degradation but also mediates its transcription termination, thus preventing lncRNA transcription from invading and repressing the downstream gene encoding a mitogen-activated protein kinase kinase kinase (MAPKKK) essential to sexual differentiation...
August 1, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28762517/immunoaffinity-based-methods-are-superior-to-kits-for-purification-of-prostate-derived-extracellular-vesicles-from-plasma-samples
#10
Sabine I Brett, Fabrice Lucien, Charles Guo, Karla C Williams, Yohan Kim, Paul N Durfee, C J Brinker, Joseph I Chin, Jun Yang, Hon S Leong
BACKGROUND: The ability to isolate extracellular vesicles (EVs) such as exosomes or microparticles is an important method that is currently not standardized. While commercially available kits offer purification of EVs from biofluids, such purified EV samples will also contain non-EV entities such as soluble protein and nucleic acids that could confound subsequent experimentation. Ideally, only EVs would be isolated and no soluble protein would be present in the final EV preparation. METHODS: We compared commercially available EV isolation kits with immunoaffinity purification techniques and evaluated our final EV preparations using atomic force microscopy (AFM) and nanoscale flow cytometry (NFC)...
August 1, 2017: Prostate
https://www.readbyqxmd.com/read/28754746/tumor-derived-exosomes-modulate-pd-l1-expression-in-monocytes
#11
Franziska Haderk, Ralph Schulz, Murat Iskar, Laura Llaó Cid, Thomas Worst, Karolin V Willmund, Angela Schulz, Uwe Warnken, Jana Seiler, Axel Benner, Michelle Nessling, Thorsten Zenz, Maria Göbel, Jan Dürig, Sven Diederichs, Jérôme Paggetti, Etienne Moussay, Stephan Stilgenbauer, Marc Zapatka, Peter Lichter, Martina Seiffert
In chronic lymphocytic leukemia (CLL), monocytes and macrophages are skewed toward protumorigenic phenotypes, including the release of tumor-supportive cytokines and the expression of immunosuppressive molecules such as programmed cell death 1 ligand 1 (PD-L1). To understand the mechanism driving protumorigenic skewing in CLL, we evaluated the role of tumor cell-derived exosomes in the cross-talk with monocytes. We carried out RNA sequencing and proteome analyses of CLL-derived exosomes and identified noncoding Y RNA hY4 as a highly abundant RNA species that is enriched in exosomes from plasma of CLL patients compared with healthy donor samples...
July 28, 2017: Science Immunology
https://www.readbyqxmd.com/read/28753793/micrornas-in-serum-exosomes-as-potential-biomarkers-in-clear-cell-renal-cell-carcinoma
#12
Wei Zhang, Maowei Ni, Ying Su, Hua Wang, Shaoxin Zhu, An Zhao, Guorong Li
BACKGROUND: Circulating microRNAs (miRNAs) in exosomes are emerging as clinically useful tools for cancer detection. However, little is known about their diagnostic impact in clear-cell renal cell carcinoma (ccRCC). OBJECTIVE: To investigate whether miRNAs in serum exosomes can serve as biomarkers in ccRCC. DESIGN, SETTING, AND PARTICIPANTS: Serum samples were obtained from 82 patients with ccRCC and 80 healthy volunteers. Exosomes were extracted and purified to selectively capture exosomes positive for tumor-associated epithelial cell adhesion molecule (EpCAM) via a magnetic bead technique...
October 14, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28753577/diagnostic-potential-of-serum-exosomal-colorectal-neoplasia-differentially-expressed-long-non-coding-rna-crnde-p-and-microrna-217-expression-in-colorectal-carcinoma
#13
Bo Yu, Qiong Du, Huan Li, Hong-Yue Liu, Xuan Ye, Bin Zhu, Qing Zhai, Xin-Xiang Li
In this study, we investigated the diagnostic potential of serum exosomal colorectal neoplasia differentially expressed (CRNDE-p) long coding RNA and microRNA-217 in colorectal carcinoma (CRC). We detected high CRNDE-p and low miR-217 levels in exosomes released by multiple CRC cell lines into culture media as well as in sera from CRC xenograft mice and CRC patients. Conversely, we observed lower CRNDE-p and higher miR-217 levels in serum exosomes from post-chemotherapy than from pre-chemotherapy patient samples...
July 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28751214/glycan-profiling-analysis-using-evanescent-field-fluorescence-assisted-lectin-array-importance-of-sugar-recognition-for-cellular-uptake-of-exosomes-from-mesenchymal-stem-cells
#14
Asako Shimoda, Yoshiro Tahara, Shin-Ichi Sawada, Yoshihiro Sasaki, Kazunari Akiyoshi
Studies involving the functional analysis of exosomal contents including proteins, DNA, and RNA have been reported. Most membrane proteins and lipids are glycosylated, which controls their physical properties and functions, but little is known about glycans on exosomes owing to the difficulty of analysing them. To shed light on these issues, we collected exosomes from mesenchymal stem cells (MSCs) derived from human adipose tissue for glycan profiling using evanescent-field fluorescence-assisted lectin array as well as analysis of their uptake in vivo...
July 24, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28748475/next-generation-sequencing-to-investigate-urinary-micrornas-from-macaca-fascicularis-cynomolgus-monkey
#15
Yaligara Veeranagouda, Jean-François Léonard, Jean-Charles Gautier, Eric Boitier
Advanced sequencing technologies like next-generation sequencing (NGS) not only detect microRNAs (miRNAs) in biological samples but also facilitate de novo identification of miRNAs. Using an Ion Torrent's Ion Proton System, here we described miRNAs sequencing of urine samples collected from Macaca fascicularis (Cynomolgus monkey) to investigate miRNAs as potential novel biomarkers of nephrotoxicity in this species. Urinary miRNA sequencing methodologies described here include (a) urinary exosomal RNA isolation, (b) sequencing library preparation, (c) sequencing template preparation, and (d) template library sequencing using Ion Proton System...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28748221/rna-substrate-length-as-an-indicator-of-exosome-interactions-in-vivo
#16
Clémentine Delan-Forino, Claudia Schneider, David Tollervey
Background: The exosome complex plays key roles in RNA processing and degradation in Eukaryotes and Archaea. Outstanding structural studies identified multiple pathways for RNA substrates into the exosome in vitro, but identifying the pathway followed by individual RNA species in vivo remains challenging. Methods: We attempted to address this question using RNase protection. In vivo RNA-protein crosslinking (CRAC) was applied to the exosome component Rrp44/Dis3, which has both endonuclease and exonuclease activity...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28745363/novel-nanosensing-technologies-for-exosome-detection-and-profiling
#17
REVIEW
Hyungsoon Im, Kyungheon Lee, Ralph Weissleder, Hakho Lee, Cesar M Castro
Exosomes have recently emerged as highly promising cancer biomarkers because they are abundant in biofluids, carry proteins and RNA reflecting their originating cells and are stable over weeks. Beyond abundance and stability, detailed exosome analyses could be clinically useful for diagnosing and profiling cancers. Despite their clinical potential, simple, reliable and sensitive approaches for rapidly quantifying exosomes and their molecular information has been challenging. Therefore, there is a clear need to develop next-generation sensing technologies for exosome detection and analysis...
July 26, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28742025/structure-and-reconstitution-of-yeast-mpp6-nuclear-exosome-complexes-reveals-that-mpp6-stimulates-rna-decay-and-recruits-the-mtr4-helicase
#18
Elizabeth V Wasmuth, John C Zinder, Dimitrios Zattas, Mom Das, Christopher D Lima
Nuclear RNA exosomes catalyze a range of RNA processing and decay activities that are coordinated in part by cofactors, including Mpp6, Rrp47, and the Mtr4 RNA helicase. Mpp6 interacts with the nine-subunit exosome core, while Rrp47 stabilizes the exoribonuclease Rrp6 and recruits Mtr4, but it is less clear if these cofactors work together. Using biochemistry with Saccharomyces cerevisiae proteins, we show that Rrp47 and Mpp6 stimulate exosome-mediated RNA decay, albeit with unique dependencies on elements within the nuclear exosome...
July 25, 2017: ELife
https://www.readbyqxmd.com/read/28741379/tiny-rnas-and-their-voyage-via-extracellular-vesicles-secretion-of-bacterial-small-rna-and-eukaryotic-microrna
#19
Ji-Woong Choi, Jee-Hyun Um, Jin-Hyun Cho, Heon-Jin Lee
MicroRNAs are small non-coding RNAs that bind to the 3'-untranslated region of target mRNAs and have transcriptional or translational inhibitory function in eukaryotes. Before microRNAs were widely known, bacterial non-coding small RNAs around 50-200 nt in length were discovered whose mechanism of action resembled that of microRNAs. Recently, RNAs that are of similar size to or smaller than microRNAs have been discovered in bacteria and indeed, this class of small RNAs have been found throughout all domains of life...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28737826/comparison-of-isolation-methods-of-exosomes-and-exosomal-rna-from-cell-culture-medium-and-serum
#20
Yue-Ting Tang, Yi-Yao Huang, Lei Zheng, Si-Hua Qin, Xu-Ping Xu, Tai-Xue An, Yong Xu, Ying-Song Wu, Xiu-Mei Hu, Bao-Hong Ping, Qian Wang
Exosomes are cell-derived vesicles and are abundant in biological fluids; they contain RNA molecules which may serve as potential diagnostic biomarkers in 'precision medicine'. To promote the clinical application of exosomal RNA (exoRNA), many isolation methods must be compared and validated. Exosomes in cell culture medium (CCM) and serum may be isolated using ultracentrifugation (UC), ExoQuick or Total Exosome Isolation Reagent (TEI), and exoRNA may be extracted using TRIzol-LS, SeraMir, Total Exosome RNA Isolation (TER), HiPure Liquid RNA/miRNA kit (HLR), miRNeasy or exoRNeasy...
September 2017: International Journal of Molecular Medicine
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