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https://www.readbyqxmd.com/read/27907160/as1411-induced-growth-inhibition-of-glioma-cells-by-up-regulation-of-p53-and-down-regulation-of-bcl-2-and-akt1-via-nucleolin
#1
Ye Cheng, Gang Zhao, Siwen Zhang, Fares Nigim, Guangtong Zhou, Zhiyun Yu, Yang Song, Yong Chen, Yunqian Li
AS1411 binds nucleolin (NCL) and is the first oligodeoxynucleotide aptamer to reach phase I and II clinical trials for the treatment of several cancers. However, the mechanisms by which AS1411 targets and kills glioma cells and tissues remain unclear. Here we report that AS1411 induces cell apoptosis and cycle arrest, and inhibits cell viability by up-regulation of p53 and down-regulation of Bcl-2 and Akt1 in human glioma cells. NCL was overexpressed in both nucleus and cytoplasm in human glioma U87, U251 and SHG44 cells compared to normal human astrocytes (NHA)...
2016: PloS One
https://www.readbyqxmd.com/read/27894092/a-novel-fully-human-anti-ncl-immunornase-for-triple-negative-breast-cancer-therapy
#2
Chiara D'Avino, Dario Palmieri, Ashley Braddom, Nicola Zanesi, Cindy James, Sara Cole, Francesco Salvatore, Carlo M Croce, Claudia De Lorenzo
Breast cancer is the most common cancer in women worldwide. A new promising anti-cancer therapy involves the use of monoclonal antibodies specific for target tumor-associated antigens (TAAs). A TAA of interest for immunotherapy of Triple Negative Breast Cancer (TNBC) is nucleolin (NCL), a multifunctional protein, selectively expressed on the surface of cancer cells, which regulates the biogenesis of specific microRNAs (miRNAs) involved in tumor development and drug-resistance. We previously isolated a novel human anti-NCL scFv, called 4LB5, that is endowed with selective anti-tumor effects...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27880931/an-xist-related-small-rna-regulates-kras-g-quadruplex-formation-beyond-x-inactivation
#3
Yuli C Chang, Chien-Chih Chiu, Chung-Yee Yuo, Wen-Ling Chan, Ya-Sian Chang, Wen-Hsin Chang, Shou-Mei Wu, Han-Lin Chou, Ta-Chih Liu, Chi-Yu Lu, Wen-Kuang Yang, Jan-Gowth Chang
X-inactive-specific transcript (XIST), a long non-coding RNA, is essential for the initiation of X-chromosome inactivation. However, little is known about other roles of XIST in the physiological process in eukaryotic cells. In this study, the bioinformatics approaches revealed XIST could be processed into a small non-coding RNA XPi2. The XPi2 RNA was confirmed by a northern blot assay; its expression was gender-independent, suggesting the role of XPi2 was beyond X-chromosome inactivation. The pull-down assay combined with LC-MS-MS identified two XPi2-associated proteins, nucleolin and hnRNP A1, connected to the formation of G-quadruplex...
November 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27874146/roles-of-nucleolin-focus-on-cancer-and-anti-cancer-therapy
#4
Zhuo Chen, XinHua Xu
Nucleolin, a multifunctional protein distributed in the nucleolus, participates in many modulations including rDNA transcription, RNA metabolism, and ribosome assembly. Nucleolin is also found in the cytoplasm and on the cell membrane, and surface nucleolin can bind to various ligands to affect many physiological functions. The expression and localization of nucleolin is often abnormal in cancers, as the differential distribution of nucleolin in cancer can influence the carcinogenesis, proliferation, survival, and metastasis of cancer cells, leading to the cancer progression...
December 2016: Saudi Medical Journal
https://www.readbyqxmd.com/read/27792899/functional-alterations-of-root-meristematic-cells-of-arabidopsis-thaliana-induced-by-a-simulated-microgravity-environment
#5
Elodie Boucheron-Dubuisson, Ana I Manzano, Isabel Le Disquet, Isabel Matía, Julio Sáez-Vasquez, Jack J W A van Loon, Raúl Herranz, Eugénie Carnero-Diaz, F Javier Medina
Environmental gravity modulates plant growth and development, and these processes are influenced by the balance between cell proliferation and differentiation in meristems. Meristematic cells are characterized by the coordination between cell proliferation and cell growth, that is, by the accurate regulation of cell cycle progression and the optimal production of biomass for the viability of daughter cells after division. Thus, cell growth is correlated with the rate of ribosome biogenesis and protein synthesis...
October 19, 2016: Journal of Plant Physiology
https://www.readbyqxmd.com/read/27792779/dual-role-of-a-sas10-c1d-family-protein-in-ribosomal-rna-gene-expression-and-processing-is-essential-for-reproduction-in-arabidopsis-thaliana
#6
Ying-Jiun C Chen, Huei-Jing Wang, Guang-Yuh Jauh
In eukaryotic cells, ribosomal RNAs (rRNAs) are transcribed, processed, and assembled with ribosomal proteins in the nucleolus. Regulatory mechanisms of rRNA gene (rDNA) transcription and processing remain elusive in plants, especially their connection to nucleolar organization. We performed an in silico screen for essential genes of unknown function in Arabidopsis thaliana and identified Thallo (THAL) encoding a SAS10/C1D family protein. THAL disruption caused enlarged nucleoli in arrested embryos, aberrant processing of precursor rRNAs at the 5' External Transcribed Spacer, and repression of the major rDNA variant (VAR1)...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27754848/nucleolin-targeting-impairs-the-progression-of-pancreatic-cancer-and-promotes-the-normalization-of-tumor-vasculature
#7
Maud-Emmanuelle Gilles, Federica Maione, Mélissande Cossutta, Gilles Carpentier, Laure Caruana, Sylvia Di Maria, Claire Houppe, Damien Destouches, Ksenya Shchors, Christopher Prochasson, Fabien Mongelard, Simona Lamba, Alberto Bardelli, Philippe Bouvet, Anne Couvelard, José Courty, Enrico Giraudo, Ilaria Cascone
Pancreatic cancer is a highly aggressive tumor, mostly resistant to the standard treatments. Nucleolin (NCL) is overexpressed in cancers and its inhibition impairs tumor growth. Herein we showed that NCL was overexpressed in human specimens of pancreatic ductal adenocarcinoma (PDAC) and that the overall survival significantly increased in patients with low levels of NCL. The NCL antagonist N6L strongly impaired the growth of primary tumors and liver metastasis in an orthotopic mouse model of PDAC (mPDAC). Similar anti-tumor effect of N6L has been observed in a highly angiogenic mouse model of pancreatic neuroendocrine tumor RIP-Tag2...
October 17, 2016: Cancer Research
https://www.readbyqxmd.com/read/27711134/interaction-of-host-nucleolin-with-influenza-a-virus-nucleoprotein-in-the-early-phase-of-infection-limits-the-late-viral-gene-expression
#8
Deepshikha Kumar, Shobha Broor, Maitreyi S Rajala
Influenza A virus nucleoprotein, is a multifunctional RNA-binding protein, encoded by segment-5 of the negative sense RNA genome. It serves as a key connector between the virus and the host during virus replication. It continuously shuttles between the cytoplasm and the nucleus interacting with various host cellular factors. In the current study, host proteins interacting with nucleoprotein of Influenza A virus of H1N1 2009 pandemic strain were identified by co-immunoprecipitation studies followed by MALDI-TOF/MS analysis...
2016: PloS One
https://www.readbyqxmd.com/read/27702507/fabrication-of-aptamer-decorated-dextran-coated-nano-graphene-oxide-for-targeted-drug-delivery
#9
Mona Alibolandi, Marzieh Mohammadi, Seyed Mohammad Taghdisi, Mohammad Ramezani, Khalil Abnous
In the current study, dextran (DEX) was covalently conjugated to the surface of nano-GO sheets, making stable biocompatible dextran coated GO (GO-DEX). The prepared GO-DEX was nontoxic to 4T1 mammary carcinoma cell line at concentrations up to 300μg/mL. AS1411 aptamer, a ssDNA aptamer which can improve the intracellular uptake by nucleolin recognition, also has been introduced to hydroxyl groups of DEX in GO-DEX to produce GO-DEX-Apt. Moreover, curcumin (CUR), a natural polyphenol, found in the rhizomes of Curcuma longa (turmeric) which shows antineoplastic effects, was loaded onto the GO-DEX and GO-DEX-Apt via π-π stacking interactions with a high loading capacity (∼29wt%)...
January 2, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/27693125/pleiotrophin-and-its-receptor-protein-tyrosine-phosphatase-beta-zeta-as-regulators-of-angiogenesis-and-cancer
#10
REVIEW
Evangelia Papadimitriou, Evangelia Pantazaka, Penelope Castana, Thomas Tsalios, Alexandros Polyzos, Dimitris Beis
Pleiotrophin (PTN) is a secreted heparin-binding growth factor that through its receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) has a significant regulatory effect on angiogenesis and cancer. PTN and RPTPβ/ζ are over-expressed in several types of human cancers and regulate important cancer cell functions in vitro and cancer growth in vivo. This review begins with a brief introduction of PTN and the regulation of its expression. PTN receptors are described with special emphasis on RPTPβ/ζ, which also interacts with and/or affects the function of other important targets for cancer therapy, such as vascular endothelial growth factor A, ανβ3 and cell surface nucleolin...
September 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27673355/nucleolin-and-nucleophosmin-nucleolar-proteins-with-multiple-functions-in-dna-repair
#11
Daniel D Scott, Marlene Oeffinger
The nucleolus represents a highly multifunctional intranuclear organelle in which, in addition to the canonical ribosome assembly, numerous processes such as transcription, DNA repair and replication, the cell cycle, and apoptosis are coordinated. The nucleolus is further a key hub in the sensing of cellular stress and undergoes major structural and compositional changes in response to cellular perturbations. Numerous nucleolar proteins have been identified that, upon sensing nucleolar stress, deploy additional, non-ribosomal roles in the regulation of varied cell processes including cell cycle arrest, arrest of DNA replication, induction of DNA repair, and apoptosis, among others...
October 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/27669098/a-mechanosensor-mechanism-controls-the-g-quadruplex-i-motif-molecular-switch-in-the-myc-promoter-nhe-iii1
#12
Caleb Sutherland, Yunxi Cui, Hanbin Mao, Laurence H Hurley
MYC is overexpressed in many different cancer types and is an intensively studied oncogene because of its contributions to tumorigenesis. The regulation of MYC is complex, and the NHE III1 and FUSE elements rely upon noncanonical DNA structures and transcriptionally induced negative superhelicity. In the NHE III1 only the G-quadruplex has been extensively studied, whereas the role of the i-motif, formed on the opposite C-rich strand, is much less understood. We demonstrate here that the i-motif is formed within the 4CT element and is recognized by hnRNP K, which leads to a low level of transcription activation...
October 11, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27644794/plant-nucleolar-dna-green-light-shed-on-the-role-of-nucleolin-in-genome-organization
#13
Claire Picart, Frédéric Pontvianne
The nucleolus forms as a consequence of ribosome biogenesis, but it is also implicated in other cell functions. The identification of nucleolus-associated chromatin domains (NADs) in animal and plant cells revealed the presence of DNA sequences other than rRNA genes in and around the nucleolus. NADs display repressive chromatin signatures and harbour repetitive DNA, but also tRNA genes and RNA polymerase II-transcribed genes. Furthermore, the identification of NADs revealed a specific function of the nucleolus and the protein Nucleolin 1 (NUC1) in telomere biology...
September 20, 2016: Nucleus
https://www.readbyqxmd.com/read/27602772/c-myc-targeted-regulators-of-cell-metabolism-in-a-transgenic-mouse-model-of-papillary-lung-adenocarcinoma
#14
Yari Ciribilli, Prashant Singh, Alberto Inga, Jürgen Borlak
c-Myc's role in pulmonary cancer metabolism is uncertain. We therefore investigated c-Myc activity in papillary lung adenocarcinomas (PLAC). Genomics revealed 90 significantly regulated genes (> 3-fold) coding for cell growth, DNA metabolism, RNA processing and ribosomal biogenesis and bioinformatics defined c-Myc binding sites (TFBS) at > 95% of up-regulated genes. EMSA assays at 33 novel TFBS evidenced DNA binding activity and ChIP-seq data retrieved from public repositories confirmed these to be c-Myc bound...
September 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27594091/synthesis-and-evaluation-of-an-18-f-labeled-derivative-of-f3-for-targeting-surface-expressed-nucleolin-in-cancer-and-tumor-endothelial-cells
#15
Phoebe Y H Lam, Christopher R T Hillyar, Sarah Able, Katherine A Vallis
The surface overexpression of nucleolin provides an anchor for the specific attachment of biomolecules to cancer and angiogenic endothelial cells. The peptide F3 is a high-affinity ligand of the nucleolin receptor (NR) that has been investigated as a carrier to deliver biologically active molecules to tumors for both therapeutic and imaging applications. A site-specific PEGylated F3 derivative was radiolabeled with [(18) F]Al-F. The binding affinity and cellular distribution of the compound was assessed in tumor (H2N) and tumor endothelial (2H-11) cells...
October 2016: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/27574784/nucleolin-aptamer-therapy-in-retinoblastoma-molecular-changes-and-mass-spectrometry-based-imaging
#16
Nithya Subramanian, Amitava Srimany, Jagat R Kanwar, Rupinder K Kanwar, Balachandran Akilandeswari, Pukhraj Rishi, Vikas Khetan, Madavan Vasudevan, Thalappil Pradeep, Subramanian Krishnakumar
Retinoblastoma (RB) is an intraocular childhood tumor which, if left untreated, leads to blindness and mortality. Nucleolin (NCL) protein which is differentially expressed on the tumor cell surface, binds ligands and regulates carcinogenesis and angiogenesis. We found that NCL is over expressed in RB tumor tissues and cell lines compared to normal retina. We studied the effect of nucleolin-aptamer (NCL-APT) to reduce proliferation in RB tumor cells. Aptamer treatment on the RB cell lines (Y79 and WERI-Rb1) led to significant inhibition of cell proliferation...
2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27550088/obtaining-more-accurate-signals-spatiotemporal-imaging-of-cancer-sites-enabled-by-a-photoactivatable-aptamer-based-strategy
#17
Heng Xiao, Yuqi Chen, Erfeng Yuan, Wei Li, Zhuoran Jiang, Lai Wei, Haomiao Su, Weiwu Zeng, Yunjiu Gan, Zijing Wang, Bifeng Yuan, Shanshan Qin, Xiaohua Leng, Xin Zhou, Songmei Liu, Xiang Zhou
Early cancer diagnosis is of great significance to relative cancer prevention and clinical therapy, and it is crucial to efficiently recognize cancerous tumor sites at the molecular level. Herein, we proposed a versatile and efficient strategy based on aptamer recognition and photoactivation imaging for cancer diagnosis. This is the first time that a visible light-controlled photoactivatable aptamer-based platform has been applied for cancer diagnosis. The photoactivatable aptamer-based strategy can accurately detect nucleolin-overexpressed tumor cells and can be used for highly selective cancer cell screening and tissue imaging...
September 14, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27542246/nucleolin-binding-by-erbb2-enhances-tumorigenicity-of-erbb2-positive-breast-cancer
#18
Eya Wolfson, Maria Goldenberg, Shira Solomon, Amit Frishberg, Ronit Pinkas-Kramarski
ErbB2 is an important member of the ErbB family, which activates growth and proliferation signaling pathways. ErbB2 is often overexpressed in various malignancies, especially in breast cancer, and is a common target for anti-cancer drugs. Breast cancer is currently one of the leading mortality causes in women, and acquired resistance to ErbB2-targeted therapies is a major obstacle in its treatment. Thus, understanding ErbB2-mediated signaling is crucial for further development of anti-cancer therapeutics and disease treatment...
August 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27525972/a-hybrid-chalcone-combining-the-trimethoxyphenyl-and-isatinyl-groups-targets-multiple-oncogenic-proteins-and-pathways-in-hepatocellular-carcinoma-cells
#19
Lili Cao, Lijun Zhang, Xiang Zhao, Ye Zhang
Small molecule inhibitors that can simultaneously inhibit multiple oncogenic proteins in essential pathways are promising therapeutic chemicals for hepatocellular carcinoma (HCC). To combine the anticancer effects of combretastatins, chalcones and isatins, we synthesized a novel hybrid molecule 3',4',5'-trimethoxy-5-chloro-isatinylchalcone (3MCIC). 3MCIC inhibited proliferation of cultured HepG2 cells, causing rounding-up of the cells and massive vacuole accumulation in the cytoplasm. Paxillin and focal adhesion plaques were downregulated by 3MCIC...
2016: PloS One
https://www.readbyqxmd.com/read/27494117/modified-as1411-aptamer-suppresses-hepatocellular-carcinoma-by-up-regulating-galectin-14
#20
Yuri Cho, Yun Bin Lee, Jeong-Hoon Lee, Dong Hyeon Lee, Eun Ju Cho, Su Jong Yu, Yoon Jun Kim, Jong In Kim, Jong Hun Im, Jung Hwan Lee, Eun Ju Oh, Jung-Hwan Yoon
Aptamers are small synthetic oligonucleotides that bind to target proteins with high specificity and affinity. AS1411 is an aptamer that binds to nucleolin, which is overexpressed in the cytoplasm and occurs on the surface of cancer cells. We investigated the therapeutic potential of aptamers in hepatocellular carcinoma (HCC) by evaluating anti-tumor effects and confirming the affinity and specificity of AS1411- and modified AS1411-aptamers in HCC cells. Cell growth was assessed using the MTS assay, and cell death signaling was explored by immunoblot analysis...
2016: PloS One
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