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https://www.readbyqxmd.com/read/28827400/upf1-helicase-promotes-tsn-mediated-mirna-decay
#1
Reyad A Elbarbary, Keita Miyoshi, Omar Hedaya, Jason R Myers, Lynne E Maquat
While microRNAs (miRNAs) regulate the vast majority of protein-encoding transcripts, little is known about how miRNAs themselves are degraded. We recently described Tudor-staphylococcal/micrococcal-like nuclease (TSN)-mediated miRNA decay (TumiD) as a cellular pathway in which the nuclease TSN promotes the decay of miRNAs that contain CA and/or UA dinucleotides. While TSN-mediated degradation of either protein-free or AGO2-loaded miRNAs does not require the ATP-dependent RNA helicase UPF1 in vitro, we report here that cellular TumiD requires UPF1...
August 21, 2017: Genes & Development
https://www.readbyqxmd.com/read/28827335/cellular-cap-binding-protein-eif4e-promotes-picornavirus-genome-restructuring-and-translation
#2
Brian C Avanzino, Gabriele Fuchs, Christopher S Fraser
Picornaviruses use internal ribosome entry sites (IRESs) to translate their genomes into protein. A typical feature of these IRESs is their ability to bind directly to the eukaryotic initiation factor (eIF) 4G component of the eIF4F cap-binding complex. Remarkably, the hepatitis A virus (HAV) IRES requires eIF4E for its translation, but no mechanism has been proposed to explain this. Here we demonstrate that eIF4E regulates HAV IRES-mediated translation by two distinct mechanisms. First, eIF4E binding to eIF4G generates a high-affinity binding conformation of the eIF4F complex for the IRES...
August 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28819455/microvesicles-as-potential-biomarkers-for-the-identification-of-senescence-in-human-mesenchymal-stem-cells
#3
Qian Lei, Teng Liu, Fei Gao, Hui Xie, Li Sun, Aiqi Zhao, Wenxiang Ren, Hao Guo, Liming Zhang, Hongxiang Wang, Zhichao Chen, An-Yuan Guo, Qiubai Li
Senescence in human mesenchymal stem cells (MSCs) not only contributes to organism aging and the development of a variety of diseases but also severely impairs their therapeutic properties as a promising cell therapy. Studies searching for efficient biomarkers that represent cellular senescence have attracted much attention; however, no single marker currently provides an accurate cell-free representation of cellular senescence. Here, we studied characteristics of MSC-derived microvesicles (MSC-MVs) that may reflect the senescence in their parental MSCs...
2017: Theranostics
https://www.readbyqxmd.com/read/28819405/linc00152-promotes-cancer-cell-proliferation-and-invasion-and-predicts-poor-prognosis-in-lung-adenocarcinoma
#4
Pei-Pei Zhang, Yi-Qin Wang, Wei-Wei Weng, Wei Nie, Yong Wu, Yu Deng, Ping Wei, Mi-Die Xu, Chao-Fu Wang
Background: The long non-coding RNA Linc00152 stimulates tumor progression in cancer. However, its clinical significance and biological functions in lung adenocarcinoma remains unknown. We evaluate the expression of Linc00152 in lung adenocarcinoma and its possible correlation with clinicopathologic features and patient survival to reveal its biological effects in cancer progression and prognosis. Methods: Total RNA extraction was performed on 110 pairs of lung adenocarcinoma and adjacent normal tissue samples, and then RT-qPCR was conducted...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819235/expression-of-long-non-coding-rna-mfi2-as1-is-a-strong-predictor-of-recurrence-in-sporadic-localized-clear-cell-renal-cell-carcinoma
#5
Ronan Flippot, Roger Mouawad, Jean-Philippe Spano, Morgan Rouprêt, Eva Compérat, Marc-Olivier Bitker, Jérôme Parra, Christophe Vaessen, Frederick Allanic, Quentin Manach, Nizar M Tannir, David Khayat, Xiaoping Su, Gabriel G Malouf
Prediction of recurrence is a challenge for the development of adjuvant treatments in clear-cell renal cell carcinoma (ccRCC). In these tumors, expression of long non-coding RNAs (lncRNAs) are deregulated and closely associated with prognosis. Thus, we aimed to predict ccRCC recurrence risk using lncRNA expression. We identified prognostic lncRNAs in a training set of 351 localized ccRCCs from The Cancer Genome Atlas and validated lncRNA-based recurrence classification in an independent cohort of 167 localized ccRCCs...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28817603/expression-of-the-mhc-class-ii-in-triple-negative-breast-cancer-is-associated-with-tumor-infiltrating-lymphocytes-and-interferon-signaling
#6
In Ah Park, Seong-Hye Hwang, In Hye Song, Sun-Hee Heo, Young-Ae Kim, Won Seon Bang, Hye Seon Park, Miseon Lee, Gyungyub Gong, Hee Jin Lee
Tumor-infiltrating lymphocytes (TILs) have been known for their strong prognostic and predictive significance in triple-negative breast cancer (TNBC). Several mechanisms for TIL influx in TNBC have been elucidated. Major histocompatibility complex class II (MHC-II) is an essential component of the adaptive immune system and is generally restricted to the surface of antigen-presenting cells. However, it has been reported that interferon-gamma signaling may induce MHC-II in almost all cell types, including those derived from cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28816616/transfer-rna-mediated-enhancement-of-ribosomal-proteins-s6-kinases-signalling-for-cell-proliferation
#7
Nam Hoon Kwon, Mi Ran Lee, Jiwon Kong, Seung Kyun Park, Byung Joon Hwang, Byung Gyu Kim, Eun-Shin Lee, Hyeong-Gon Moon, Sunghoon Kim
While transfer RNAs (tRNAs) are known to transport amino acids to ribosome, new functions are being unveiled from tRNAs and their fragments beyond protein synthesis. Here we show that phosphorylation of 90-kDa RPS6K (ribosomal proteins S6 kinase) was enhanced by tRNA(Leu) overexpression under amino acids starvation condition. The phosphorylation of 90-kDa RPS6K was decreased by siRNA specific to tRNA(Leu) and was independent to mTOR (mammalian target of rapamycin) signalling. Among the 90-kDa RPS6K family, RSK1 (ribosomal S6 kinase 1) and MSK2 (mitogen-and stress-activated protein kinase 2) were the major kinases phosphorylated by tRNA(Leu) overexpression...
August 17, 2017: RNA Biology
https://www.readbyqxmd.com/read/28815582/activation-of-twist1-by-col11a1-promotes-chemoresistance-and-inhibits-apoptosis-in-ovarian-cancer-cells-by-modulating-nf-%C3%AE%C2%BAb-mediated-ikk%C3%AE-expression
#8
Yi-Hui Wu, Yu-Fang Huang, Tzu-Hao Chang, Cheng-Yang Chou
We have shown that collagen type XI alpha 1 (COL11A1) promotes ovarian cancer progression and is associated with chemoresistance to cisplatin and paclitaxel in ovarian cancer cells. Here, we demonstrate how COL11A1 regulates twist family basic helix-loop-helix transcription factor 1-related protein 1 (TWIST1) to induce chemoresistance and inhibit apoptosis in ovarian cancer cells. Small interfering RNA-mediated reduction in COL11A1 protein levels increased the chemosensitivity to cisplatin and paclitaxel via downregulated TWIST1 expression...
August 17, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28814526/hiv-1-exploits-dynamic-multi-aminoacyl-trna-synthetase-complex-to-enhance-viral-replication
#9
Alice A Duchon, Corine St-Gelais, Nathan Titkemeier, Joshua Hatterschide, Li Wu, Karin Musier-Forsyth
A hallmark of retroviruses such as human immunodeficiency virus type 1 (HIV-1) is reverse transcription of genomic RNA to DNA, a process that is primed by cellular tRNAs. HIV-1 recruits human tRNA(Lys3) to serve as the reverse transcription primer via an interaction between lysyl-tRNA synthetase (LysRS) and the HIV-1 Gag polyprotein. LysRS is normally sequestered in a multi-aminoacyl-tRNA synthetase complex (MSC). Previous studies demonstrated that components of the MSC can be mobilized in response to certain cellular stimuli, but how LysRS is redirected from the MSC to viral particles for packaging is unknown...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28808919/backbone-and-side-chain-assignments-of-the-second-rna-binding-domain-of-musashi-1-in-its-free-form-and-in-complex-with-5-mer-rna
#10
Ryo Iwaoka, Takashi Nagata, Kengo Tsuda, Takao Imai, Hideyuki Okano, Naohiro Kobayashi, Masato Katahira
Musashi1 (Msi1) is an RNA-binding protein that is involved in cell fate determination. Here, we report the (1)H, (15)N, and (13)C resonance assignments of Msi1 second RNA-binding domain in free form and in complex with RNA. The assignments can be utilized for NMR structure and dynamics analyses of the Msi1:RNA complex, and moreover, for chemical shift perturbation analyses to evaluate the binding of potential small molecule inhibitors against Msi1:RNA interaction.
August 14, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28808873/elevated-hu-antigen-receptor-hur-expression-is-associated-with-tumor-aggressiveness-and-poor-prognosis-but-not-with-cox-2-expression-in-invasive-breast-carcinoma-patients
#11
Constantinos Giaginis, Anastasia Sampani, Iolly Kotta-Loizou, Ioanna Giannopoulou, Eugene Danas, Ekaterini Politi, Gerasimos Tsourouflis, Gregorios Kouraklis, Efstratios Patsouris, Antonios Keramopoulos, Lydia Nakopoulou, Stamatios Theocharis
Hu-antigen R (HuR), a RNA-binding protein, is considered to play a crucial role in tumor development and progression by stabilizing or regulating a group of cellular mRNAs of cancer-related genes, such as cyclooxygenase-2 (COX-2). The present study aimed to evaluate the clinical significance of HuR and COX-2 expression in invasive breast carcinoma. HuR and COX-2 protein expression was assessed immunohistochemically on paraffin-embedded breast cancer tissue sections obtained from 121 patients and was statistically analyzed with clinicopathological parameters, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as with tumor cells' proliferative capacity and overall and disease-free patients' survival...
August 14, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28805673/alk-status-assessment-with-liquid-biopsies-of-lung-cancer-patients
#12
REVIEW
Paul Hofman
Patients with advanced stage non-small cell lung carcinoma (NSCLC) harboring an anaplastic lymphoma kinase ALK gene rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. However, while treatment is initially effective in most cases, relapse or progression occurs due to different resistance mechanisms including mutations in the tyrosine kinase domain of echinoderm microtubule-associated protein-like 4 (EML44)-ALK. The liquid biopsy concept has recently radically changed the clinical care of NSCLC patients, in particular for those harboring an epidermal growth factor receptor (EGFR) gene mutation...
August 12, 2017: Cancers
https://www.readbyqxmd.com/read/28805106/measuring-fetal-brain-and-lung-transcripts-in-amniotic-fluid-supernatant-a-comparison-of-digital-pcr-and-rt-qpcr-methods
#13
Lisa Hui, Sally Beard, Natalie J Hannan
PURPOSE: Amniotic fluid (AF) cell-free RNA is a promising source of information regarding fetal physiology. Digital PCR (dPCR) is a direct approach to nucleic acid detection that reports absolute transcript copy number. The aim of this study was to compare quantification of cell-free fetal brain and lung RNA transcripts in AF by reverse transcription-qPCR and dPCR. MATERIAL AND METHODS: Prospective hospital-based study performed in 2016-2017. Pulmonary genes were quantified in term AF samples collected at elective cesarean birth; neurodevelopmental genes were measured in preterm samples (< 34 weeks) obtained from women undergoing clinically-indicated amniocentesis...
August 14, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28802563/metabolic-circuit-involving-free-fatty-acids-microrna-122-and-triglyceride-synthesis-in-liver-and-muscle-tissues
#14
Chofit Chai, Mila Rivkin, Liav Berkovits, Alina Simerzin, Elina Zorde-Khvalevsky, Nofar Rosenberg, Shiri Klein, Dayana Yaish, Ronen Durst, Shoshana Shpitzen, Shiran Udi, Joseph Tam, Joerg Heeren, Anna Worthmann, Christoph Schramm, Johannes Kluwe, Revital Ravid, Eran Hornstein, Hilla Giladi, Eithan Galun
BACKGROUND & AIMS: Effective treatments are needed for hepatic steatosis characterized by accumulation of triglycerides in hepatocytes, which leads to hepatocellular carcinoma. MicroRNA 122 (MIR122) is expressed only in the liver, where it regulates lipid metabolism. We investigated the mechanism by which free fatty acids (FFAs) regulate MIR122 expression and the effect of MIR122 on triglyceride synthesis. METHODS: We analyzed MIR122 promoter activity and validated its target mRNAs by transfection of luciferase reporter plasmids into Huh7, BNL-1ME, and HEK293 cultured cell lines...
August 9, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28791397/trpc1-stimulates-calcium%C3%A2-sensing-receptor%C3%A2-induced-store%C3%A2-operated-ca2-entry-and-nitric-oxide-production-in-endothelial-cells
#15
Yuan-Yuan Qu, La-Mei Wang, Hua Zhong, Yong-Min Liu, Na Tang, Li-Ping Zhu, Fang He, Qing-Hua Hu
Store‑operated Ca2+ entry (SOCE) via store‑operated Ca2+ channels (SOCC), encoded by transient receptor potential canonical (TRPC) channel proteins, is an important underlying mechanism regulating intracellular Ca2+ concentration ([Ca2+]i) and various intracellular functions in endothelial cells (ECs). TRPC1, the probable candidate for SOCC, is expressed in ECs. Ca2+‑sensing receptor (CaSR) is functionally expressed in vascular endothelium and is important in Ca2+ mobilization and cardiovascular functions...
August 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28790236/-1-10-phenanthroline-based-cyanine-dyes-as-fluorescent-probes-for-ribonucleic-acids-in-live-cells
#16
Vladyslava Kovalska, Marina Kuperman, Oleg Varzatskii, Dmytro Kryvorotenko, Elisa Kinski, Margot Schikora, Christina Janko, Christoph Alexiou, Sergiy Yarmoluk, Andriy Mokhir
A series of monomethine, trimethine- and styrylcyanine dyes based on a [1,10]phenanthroline moiety was synthesized, characterized and investigated as potential fluorescent probes for nucleic acids in cell free settings and in cells. The dyes were found to be weakly fluorescent in the unbound state, whereas upon the binding to dsDNA or RNA their emission intensity raised up to 50 times (for monomethine benzothiazole derivative FT1 complexed with RNA). The strongest fluorescence intensity in assemblies with dsDNA and RNA was observed for the trimethine benzothiazole derivative FT4...
August 9, 2017: Methods and Applications in Fluorescence
https://www.readbyqxmd.com/read/28782577/down-regulation-of-long-non-coding-rna-meg3-indicates-an-unfavorable-prognosis-in-non-small-cell-lung-cancer-evidence-from-the-geo-database
#17
Zichao Zhang, Tiantian Liu, Kai Wang, Xiao Qu, Zhaofei Pang, Shaorui Liu, Qi Liu, Jiajun Du
Long non-coding RNA (lncRNA) MEG3 (maternally expressed gene 3) is an imprinted gene that suppresses cells growth in various tumors. However, the association between MEG3 expression and prognosis in non-small cell lung cancer (NSCLC) has not been fully investigated. Seven datasets with 1144 patients were obtained from Gene Expression Omnibus (GEO) database (Affymetrix U133 Plus 2.0 platform). Association between MEG3 and other variables was tested using the chi-squared test. Kaplan-Meier survival analysis was carried out to explore the association between MEG3 expression and overall survival (OS)/progression free survival (PFS)...
August 3, 2017: Gene
https://www.readbyqxmd.com/read/28782251/hcv-plays-with-fire-and-yet-avoids-getting-burned-a-review-for-clinicians-on-processing-bodies-and-stress-granules
#18
Carlos Fernández-Carrillo, Gemma Pérez-Vilaró, Juana Díez, Sofía Pérez-Del-Pulgar
Over the last few years, many reports have defined several types of RNA cell granules composed of proteins and messenger RNA (mRNA) that regulate gene expression on a posttranscriptional level. Processing bodies (P-bodies) and stress granules (SGs) are among the best-known RNA granules, only detectable when they accumulate into very dynamic cytosolic foci. Recently, a tight association has been found between positive-stranded RNA viruses, including hepatitis C virus (HCV), and these granules. The present article offers a comprehensive review on the complex and paradoxical relationship between HCV, P-bodies and SGs from a translational perspective...
August 7, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28770558/long-non-coding-rna-malat1-is-an-inducible-stress-response-gene-associated-with-extramedullary-spread-and-poor-prognosis-of-multiple-myeloma
#19
Hiroshi Handa, Yuko Kuroda, Kei Kimura, Yuta Masuda, Hikaru Hattori, Lobna Alkebsi, Morio Matsumoto, Tetsuhiro Kasamatsu, Nobuhiko Kobayashi, Ken-Ichi Tahara, Makiko Takizawa, Hiromi Koiso, Takuma Ishizaki, Hiroaki Shimizu, Akihiko Yokohama, Norifumi Tsukamoto, Takayuki Saito, Hirokazu Murakami
Extramedullary myeloma (EMM) occurs when myeloma develops outside the bone marrow; it often develops after chemotherapy and is associated with the acquisition of chemo-resistance and a fatal course. The mechanisms underlying extramedullary spread have not yet been fully elucidated. MALAT1 is a highly abundantly and ubiquitously expressed long non-coding RNA that plays important roles in cancer metastasis. The aims of this study were to clarify the association of MALAT1 with EMM and to elucidate the underlying mechanism of EMM formation under chemotherapeutic pressure...
August 2, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28768505/tough-decoy-targeting-of-predominant-let-7-mirna-species-in-adult-human-hematopoietic-cells
#20
Jaira F de Vasconcellos, Colleen Byrnes, Y Terry Lee, Joshua M Allwardt, Megha Kaushal, Antoinette Rabel, Jeffery L Miller
BACKGROUND: In humans, the heterochronic cascade composed of the RNA-binding protein LIN28 and its major target, the let-7 family of microRNAs (miRNAs), is highly regulated during human erythroid ontogeny. Additionally, down-regulation of the let-7 miRNAs in cultured adult CD34(+) cells or the over-expression of LIN28 in cultured erythrocytes from pediatric patients with HbSS genotype causes increased levels of fetal hemoglobin (HbF) in the range of 19-40% of the total. Therefore, we hypothesized that focused targeting of individual let-7 miRNA family members would exhibit regulatory effect on HbF expression in human adult erythroblasts...
August 2, 2017: Journal of Translational Medicine
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