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991.
Long noncoding RNA PVT1 promotes cervical cancer progression through epigenetically silencing miR‐200b 下载免费PDF全文
Shaorong Zhang Guanli Zhang Jingying Liu 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2016,124(8):649-658
Long noncoding RNA PVT1 has been reported to be dysregulated and play vital roles in a variety of cancers. However, the functions and molecular mechanisms of PVT1 in cervical cancer remain unclear. The objective of this study was to investigate the expression, clinical significance, biological roles, and underlying functional mechanisms of PVT1 in cervical cancer. Our results revealed that PVT1 is upregulated in cervical cancer tissues. Enhanced expression of PVT1 is associated with larger tumor size, advanced International Federation of Gynecology and Obstetrics stage, and poor prognosis of cervical cancer patients. Using gain‐of‐function and loss‐of‐function approaches, we demonstrated that overexpression of PVT1 promotes cervical cancer cells proliferation, cell cycle progression and migration, and depletion of PVT1 inhibits cervical cancer cell proliferation, cell cycle progression, and migration. Mechanistically, we verified that PVT1 binds to EZH2, recruits EZH2 to the miR‐200b promoter, increases histone H3K27 trimethylation level on the miR‐200b promoter, and inhibits miR‐200b expression. Furthermore, the effects of PVT1 on cervical cell proliferation and migration depend upon silencing of miR‐200b. Taken together, our findings confirmed that PVT1 functions as an oncogene in cervical cancer and indicated that PVT1 is not only an important prognostic marker, but also a potential therapy target for cervical cancer. 相似文献
992.
Tissue factor (TF) is a membranous glycoprotein that functions as a receptor for coagulation factor VII/VIIa and activates the coagulation system when blood vessels or tissues are damaged. TF was upregulated in our monocrotaline (MCT)/lipopolysaccharide (LPS) hepatotoxicity model. We tested the hypothesis that TF‐dependent fibrin deposition and lipid peroxidation in the form of oxidized low‐density‐lipoprotein (ox‐LDL) accumulation contribute to liver inflammation induced by MCT/LPS in mice. In the present study, we blocked TF using antisense oligodeoxynucleotides against mouse TF (TF‐ASO). TF‐ASO (5.6 mg kg?1) was given i.v. to ND4 male mice 30 min after administration of MCT (200 mg kg?1) p.o. followed after 3.5 h by LPS i.p. (6 mg kg?1). Blood alanine aminotransferase (ALT), TF, ox‐LDL, platelets, hematocrit and keratinocyte‐derived chemokine (KC) levels were evaluated in different treatment groups. Fibrin deposition and ox‐LDL accumulation were also analyzed in the liver sections using immunofluorescent staining. The results showed that TF‐ASO significantly restored blood ALT, hematocrit and KC levels, distorted after MCT/LPS co‐treatment, as well as preventing the accumulation of ox‐LDL and the deposition of fibrin in the liver tissues, and thereby inhibited liver injury caused by MCT/LPS. In a separate experiment, TF‐ASO administration significantly prolonged animal survival. The current study demonstrates that TF is associated with MCT/LPS‐induced liver injury. Administration of TF‐ASO successfully prevented this type of liver injury. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
993.
Preparations of double-stranded (ds) RNAs extracted from naturally infected Vicia faba Linn. growing in Hangzhou, Zhejiang Province, Eastern China displayed 3 dominant bands (FaR1, FaR2, and FaR3). FaR2 and FaR3
were found to be identical to the genomic dsRNAs of a recently reported Vicia cryptic virus (VCV). The positive strand of
FaR1 contained two large open reading frames (ORFs), ORF1 and ORF2. The putative proteins encoded by these ORFs were found
to have certain similarities to the putative capsid protein [ABO36237] and RNA-dependent RNA polymerase [ABC96788], respectively,
of Tomato yellow stunt virus. Thus, FaR1 may represent the genome of a new dsRNA virus, which we have named Vicia cryptic
virus M.
The GenBank Accession numbers of the sequences reported in this paper are EU605883, EU605884, and EU371896. 相似文献
994.
Abstract: In this study, we investigated whether calbindin‐D9k (CaBP‐9k) expression was regulated by melatonin during hydrogen peroxide (H2O2)‐induced cell death in rat pituitary GH3 cells. CaBP‐9k expression was increased by melatonin in a dose‐ and time‐dependent manner, indicating that CaBP‐9k expression is regulated by melatonin. Cell survival was increased approximately 27–30% where H2O2‐treated cells (0.25 or 0.5 mm ) were also incubated with 1 mm melatonin, when compared with H2O2 alone or H2O2 plus 0.5 mm melatonin. This result was consistent with 4,6‐diamidino‐2‐phenylindole staining. CaBP‐9k expression was also augmented by co‐treatment with H2O2 and 1 mm melatonin, suggesting a functional relationship between increased cell death and melatonin‐induced CaBP‐9k expression during H2O2‐mediated apoptosis. Bcl‐2‐associated protein expression increased following treatment with H2O2 alone, whereas Bcl‐2 expression was elevated following treatment with melatonin alone, or H2O2 plus melatonin. The expression of p53 was depressed by treatment with melatonin alone, or co‐treatment with H2O2 plus melatonin. These results correlated with CaBP‐9k expression levels and activation of the mitogen‐activated protein kinase/extracellular signal‐regulated kinase signaling pathway. Knockdown of CaBP‐9k expression using a small inhibitory RNA resulted in an elevation of H2O2‐induced cell death, whereas cell survival was increased in cells that overexpressed CaBP‐9k, providing additional evidence that the induction of CaBP‐9k expression may be associated with survival signaling during H2O2‐mediated oxidative cell death. CaBP‐9k appears to interact with p53, suggesting a possible role for this interaction in cell proliferation and cell cycle progression. 相似文献
995.
Kevin S. Keating Anna Marie Pyle 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(18):8177-8182
Structured RNA molecules play essential roles in a variety of cellular processes; however, crystallographic studies of such RNA molecules present a large number of challenges. One notable complication arises from the low resolutions typical of RNA crystallography, which results in electron density maps that are imprecise and difficult to interpret. This problem is exacerbated by the lack of computational tools for RNA modeling, as many of the techniques commonly used in protein crystallography have no equivalents for RNA structure. This leads to difficulty and errors in the model building process, particularly in modeling of the RNA backbone, which is highly error prone due to the large number of variable torsion angles per nucleotide. To address this, we have developed a method for accurately building the RNA backbone into maps of intermediate or low resolution. This method is semiautomated, as it requires a crystallographer to first locate phosphates and bases in the electron density map. After this initial trace of the molecule, however, an accurate backbone structure can be built without further user intervention. To accomplish this, backbone conformers are first predicted using RNA pseudotorsions and the base-phosphate perpendicular distance. Detailed backbone coordinates are then calculated to conform both to the predicted conformer and to the previously located phosphates and bases. This technique is shown to produce accurate backbone structure even when starting from imprecise phosphate and base coordinates. A program implementing this methodology is currently available, and a plugin for the Coot model building program is under development. 相似文献
996.
997.
Ying Yang LingLing Wang Chen Wang HePing Chen ZhongHui Guo YuXian Zhang & ZiYan Zhu 《Transfusion medicine (Oxford, England)》2009,19(5):235-244
In screening 87665 unrelated healthy blood donors in China, serology studies resulted in the detection of two K0 probands, both female. To explore the molecular basis of the Knull phenotype in the Chinese population, genomic DNA, total RNA, and reticulocyte RNA were subsequently prepared from the two probands, five family members of proband 1, four unrelated normal controls, and one unrelated KEL 1 control. Nucleic acids were analyzed for the KEL gene by DNA and RNA sequencing, while antigens were analyzed by flow cytometry with BRIC18, BRIC68, anti-k, and anti-Kpb . Two novel Knull alleles were identified in both probands: in exon 3, 185insT (Ser62Phe and a premature stop codon in exon 4, GenBank accession number, EF208900), and in exon 7, 715G>T (Glu239Stop, GenBank accession number EF208901). Alternative splicing patterns were observed in RNA obtained from whole blood versus from a reticulocyte fraction. Our study identified these two novel Knull alleles resulting in the Knull phenotype, the frequency of the Knull phenotype amongst Chinese mainlanders is only 0.00228%. 相似文献
998.
999.
Stephanie Hamill Sandra L. Wolin Karin M. Reinisch 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(34):15045-15050
The Trf4p/Air2p/Mtr4p polyadenylation (TRAMP) complex recognizes aberrant RNAs in Saccharomyces cerevisiae and targets them for degradation. A TRAMP subcomplex consisting of a noncanonical poly(A) RNA polymerase in the Pol ß superfamily of nucleotidyl transferases, Trf4p, and a zinc knuckle protein, Air2p, mediates initial substrate recognition. Trf4p and related eukaryotic poly(A) and poly(U) polymerases differ from other characterized enzymes in the Pol ß superfamily both in sequence and in the lack of recognizable nucleic acid binding motifs. Here we report, at 2.7-Å resolution, the structure of Trf4p in complex with a fragment of Air2p comprising two zinc knuckle motifs. Trf4p consists of a catalytic and central domain similar in fold to those of other noncanonical Pol β RNA polymerases, and the two zinc knuckle motifs of Air2p interact with the Trf4p central domain. The interaction surface on Trf4p is highly conserved across eukaryotes, providing evidence that the Trf4p/Air2p complex is conserved in higher eukaryotes as well as in yeast and that the TRAMP complex may also function in RNA surveillance in higher eukaryotes. We show that Air2p, and in particular sequences encompassing a zinc knuckle motif near its N terminus, modulate Trf4p activity, and we present data supporting a role for this zinc knuckle in RNA binding. Finally, we show that the RNA 3′ end plays a role in substrate recognition. 相似文献
1000.
Emmanuelle Vigne Aurlie Marmonier Vronique Komar Olivier Lemaire Marc Fuchs 《Virus research》2009,144(1-2):154-162
Recombination was assessed in a vineyard site in which grapevines cross-protected with mild strains GHu of Grapevine fanleaf virus (GFLV) or Ta of Arabis mosaic virus (ArMV) were superinfected with GFLV field isolates following transmission by the nematode vector Xiphinema index. The genetic structure and variability within RNA2 of isolates from grapevines co-infected with GFLV field isolates and either GFLV-GHu or ArMV-Ta were characterized to identify intra- and interspecies recombinants. Sequence analysis and phylogenetic relationships inferred intraspecies recombination among GFLV field isolates but not between field isolates and GFLV-GHu. SISCAN analysis confirmed a mosaic structure for two GFLV field isolates for which recombination sites were located in the movement protein and coat protein genes. One of the recombinants was found in eight grapevines that were in close spatial proximity within the vineyard site, suggesting its transmission by X. index. No interspecies recombination was detected between GFLV field isolates and ArMV-Ta. Altogether, our findings suggest that mild protective strains GFLV-GHu and ArMV-Ta did not assist the emergence of viable recombinants to detectable level during a 12-year cross-protection trial. To our knowledge, this is the first extensive characterization of the genetic structure and variability of virus isolates in cross-protected plants. 相似文献