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961.
Xiangling Yang William W. Du Haoran Li Fengqiong Liu Anna Khorshidi Zina Jeyapalan Rutnam Burton B. Yang 《Nucleic acids research》2013,41(21):9688-9704
MicroRNAs (miRNA) precursor (pre-miRNA) molecules can be processed to release a miRNA/miRNA* duplex. In the canonical model of miRNA biogenesis, one strand of the duplex is thought to be the biologically active miRNA, whereas the other strand is thought to be inactive and degraded as a carrier or passenger strand called miRNA* (miRNA star). However, recent studies have revealed that miRNA* strands frequently play roles in the regulatory networks of miRNA target molecules. Our recent study indicated that miR-17 transgenic mice could abundantly express both the mature miR-17-5p and the passenger strand miR-17-3p. Here, we showed that miR-17 enhanced prostate tumor growth and invasion by increasing tumor cell proliferation, colony formation, cell survival and invasion. miRNA target analysis showed that both miR-17-5p and miR-17-3p repressed TIMP metallopeptidase inhibitor 3 (TIMP3) expression. Silencing with small interfering RNA against TIMP3 promoted cell survival and invasion. Ectopic expression of TIMP3 decreased cell invasion and cell survival. Our results demonstrated that mature miRNA can function coordinately with its passenger strand, enhancing the repressive ability of a miRNA by binding the same target. Within an intricate regulatory network, this may be among the mechanisms by which miRNA can augment their regulatory capacity. 相似文献
962.
Christopher R. Cabanski Matthew D. Wilkerson Matthew Soloway Joel S. Parker Jinze Liu Jan F. Prins J. S. Marron Charles M. Perou D. Neil Hayes 《Nucleic acids research》2013,41(19):e178
Identifying variants using high-throughput sequencing data is currently a challenge because true biological variants can be indistinguishable from technical artifacts. One source of technical artifact results from incorrectly aligning experimentally observed sequences to their true genomic origin (‘mismapping’) and inferring differences in mismapped sequences to be true variants. We developed BlackOPs, an open-source tool that simulates experimental RNA-seq and DNA whole exome sequences derived from the reference genome, aligns these sequences by custom parameters, detects variants and outputs a blacklist of positions and alleles caused by mismapping. Blacklists contain thousands of artifact variants that are indistinguishable from true variants and, for a given sample, are expected to be almost completely false positives. We show that these blacklist positions are specific to the alignment algorithm and read length used, and BlackOPs allows users to generate a blacklist specific to their experimental setup. We queried the dbSNP and COSMIC variant databases and found numerous variants indistinguishable from mapping errors. We demonstrate how filtering against blacklist positions reduces the number of potential false variants using an RNA-seq glioblastoma cell line data set. In summary, accounting for mapping-caused variants tuned to experimental setups reduces false positives and, therefore, improves genome characterization by high-throughput sequencing. 相似文献
963.
Tien-Huang Lin Hsin-Ho Liu Tsung-Hsun Tsai Chi-Cheng Chen Teng-Fu Hsieh Shang-Sen Lee Yuan-Ju Lee Wen-Chi Chen Chih-Hsin Tang 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1), belongs to the CC chemokine family which is associated with the disease status and outcomes of cancers. Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to the bone. However, the effect of CCL2 on human prostate cancer cells is largely unknown. The aim of this study was to examine the role of CCL2 in integrin expression and migratory activity in prostate cancers.Methods
Prostate cancer migration was examined using Transwell, wound healing, and invasion assay. The PKCδ and c-Src phosphorylations were examined by using western blotting. The qPCR was used to examine the mRNA expression of integrins. A transient transfection protocol was used to examine AP-1 activity.Results
Stimulation of prostate cancer cell lines (PC3, DU145, and LNCaP) induced migration and expression of integrin αvβ3. Treatment of cells with αvβ3 antibody or siRNA abolished CCL2-increased cell migration. CCL2-increased migration and integrin expression were diminished by CCR2 but not by CCR4 inhibitors, suggesting that the CCR2 receptor is involved in CCL2-promoted prostate cancer migration. CCL2 activated a signal transduction pathway that includes PKCδ, c-Src, and AP-1. Reagents that inhibit specific components of this pathway each diminished the ability of CCL2 to effect cell migration and integrin expression.Conclusions
Interaction between CCL2 and CCR2 enhances migration of prostate cancer cells through an increase in αvβ3 integrin production.General significance
CCL2 is a critical factor of prostate cancer metastasis. 相似文献964.
965.
Junying Liu Xiping YanQingqing Li Guosong WangHehe Liu Jiwen WangLiang Li Xiaohui DuChunchun Han Hua He 《Journal of thermal biology》2013
Avian embryos are easily influenced by their environment during incubation. Previous studies have demonstrated that incubation temperature changes could influence muscle development and body weight, which subsequently determine the adult phenotype. The objective of this study was to investigate whether the development of immune organs in ducklings could be influenced by thermal manipulation during the middle stage of incubation. To evaluate this hypothesis, a control group was incubated under a normal temperature from E11 to E24, while the incubation temperature of the experimental group was increased by 1 °C. Our results indicated that slight changes in the incubation temperature significantly repressed the bursa of Fabricius index of the duck embryo on E25 (F1, 58=122.51, P<0.0001) and significantly repressed the spleen index of neonatal ducklings (F1, 58=74.38, P<0.0001). At 0 day posthatching (dph) and 14 dph, ducklings hatched from eggs incubated under the higher temperature had a lower percentage of globulin than the control group (F1, 10=19.97, P=0.0111; F1, 10=9.8, P=0.0352). The IFN-γ concentration of ducklings at 14 dph displayed the same trend (F1, 10=284.49, P<0.0001). These results suggested that thermal manipulation during the middle stage of incubation had a repressive effect on the development of immune organs and reduced the concentrations of serum globulin and IFN-γ. These results demonstrated that the subtle alteration of incubation temperature may weaken ducklings' immunity. 相似文献
966.
Roniel Cabrera Miguel Ararat Yiling Xu Todd Brusko Clive Wasserfall Mark A. Atkinson Lung Ji Chang Chen Liu David R. Nelson 《Cancer immunology, immunotherapy : CII》2013,62(4):737-746
Hepatocellular carcinoma (HCC) is a difficult to treat cancer characterized by poor tumor immunity with only one approved systemic drug, sorafenib. If novel combination treatments are to be developed with immunological agents, the effects of sorafenib on tumor immunity are important to understand. In this study, we investigate the impact of sorafenib on the CD4+CD25? effector T cells (Teff) and CD4+CD25+ regulatory T cells (Tregs) from patients with HCC. We isolated Teff and Treg from peripheral mononuclear cells of HCC patients to determine immune reactivity by thymidine incorporation, ELISA and flow cytometry. Teff cultured alone or with Treg were supplemented with different concentrations of sorafenib. The effects of sorafenib on Teff responses were dose-dependent. Pharmacologic doses of sorafenib decreased Teff activation by down regulating CD25 surface expression. In contrast, sub-pharmacologic concentrations of sorafenib resulted in Teff activation. These low doses of sorafenib in the Teff cultures led to a significant increase in Teff proliferation, IL2 secretion and up-regulation of CD25 expression on the cell surface. In addition, low doses of sorafenib in the suppression Teff/Treg cocultures restored Teff responses by eliminating Treg suppression. The loss of Treg suppressive function correlated with an increase in IL2 and IL6 secretion. Our findings show that sub-pharmacologic doses of sorafenib impact subsets of T cells differently, selectively increasing Teff activation while blocking Treg function. In conclusion, this study describes novel immune activating properties of low doses of sorafenib by promoting immune responsiveness in patients with HCC. 相似文献
967.
Yibo Wang Jinxing Chen Yu Zhang Lv Bin Kai Sun Weifeng Yu Jibin Liu Channa Zhang Haiqing Shen Zhihui Hou Fangfang Yu Rutai Hui 《Human genetics》2013,132(1):29-37
VKORC1 genetic polymorphisms affect warfarin dose response, aortic calcification, and the susceptibility of coronary artery disease as shown in our previous study. Little is known regarding the association of VKORC1 polymorphisms with coronary artery calcification (CAC) and the role of CAC in the association with coronary artery disease (CAD). Due to a natural haplotype block in the VKORC1 gene in Chinese, polymorphism rs2359612 was analyzed in a case–control study and a prospective study. The case–control study included 464 CAD patients with non-calcified plaque (NCP), 562 CAD patients with mixed calcified plaque (MCP), 492 subjects with calcified plaque (CP), and 521 controls. The rs2359612C was only associated with increased risk of MCP, the CAD in the presence of CAC; the odds ratio was 1.397 (95 % CI 1.008–1.937, P < 0.05), which was replicated in the second independent population. On the contrary, a negative correlation was observed between rs2359612 and log-transformed Agatston score, and rs2359612 was negatively associated with the number of calcified vessels. Moreover, in a prospective study including 849 CAD patients undergoing revascularization, rs2359612C predicted a higher incidence of cardiovascular events in MCP subgroup; the relative risk was 1.435 (95 % CI 1.008–2.041, P = 0.045), which was not observed in the NCP subgroup. We conclude that the rs2359612C was associated with a higher risk of CAD in the presence of CAC and a higher incidence of cardiovascular events in CAD patients with CAC, but a lower coronary calcification. VKORC1 polymorphisms may be associated with the endophenotype of CAD, calcification-related atherosclerosis. 相似文献
968.
The objective of this study was to analyze human fecal Lactobacillus community and its relationship with rheumatoid arthritis. Samples taken from rheumatoid arthritis (RA) patients and healthy individuals were analyzed by quantitative real-time PCR. Bacterial DNA was extracted from feces, and amplicons of the Lactobacillus-specific regions of 16S rRNA were analyzed by denaturing gradient gel electrophoresis. The richness, Shannon-Wiener index, and evenness of gut microbiota of both groups were analyzed to compare fecal Lactobacillus community structures. Results of this study demonstrated that fecal microbiota of RA patients contained significantly more Lactobacillus (10.62 ± 1.72 copies/g) than the control group (8.93 ± 1.60 copies/g). Significant increases were observed in RA patients in terms of the richness, Shannon-Wiener, and evenness measures, indicating more bacterial species, and increased bacterial diversity and abundance. These results suggest a potential relationship between Lactobacillus communities and the development and progression of rheumatoid arthritis. 相似文献
969.
Wu Song Chun-Fu Wu Ping Liu Rong-Wu Xiang Fang Wang Ying-Xu Dong Jing-Yu Yang 《Neurochemical research》2013,38(1):153-161
Uridine, a pyrimidine nucleoside, has been proposed to be a potential signaling molecule in the central nervous system. The understanding of uridine release in the brain is therefore of fundamental importance. The present study was performed to determine the characteristics of basal and morphine-induced uridine release in the striatum of freely moving mice by using the microdialysis technique. To ascertain whether extracellular uridine was derived from neuronal release, the following criteria were applied: sensitivity to (a) K+ depolarization, (b) Na+ channel blockade and (c) removal of extracellular Ca2+. Uridine levels were not greatly affected by infusion of tetrodotoxin (TTX) and were unaffected by either Ca2+-free medium or in the presence of EGTA (a calcium chelator), suggesting that basal extracellular uridine levels were maintained mainly by non-vesicular release mechanisms. In addition, both systemic and local application of morphine increased striatal uridine release. The morphine-induced release was reversed by naloxone pretreatment, but was unaffected by TTX or EGTA infusion. Moreover, co-administration of morphine and nitrobenzylthioinosine (NBTI, an inhibitor of nucleotide transporter) produced increases of uridine levels similar to that produced by NBTI or morphine alone, suggesting a nucleotide transporter mechanism involved. Taken together, these findings suggest that morphine produces a μ-opioid receptor-mediated uridine release via nucleoside transporters in a TTX- and calcium-independent manner. 相似文献
970.
Yibing Xu Jianping Sun Michael A. Sheard Hung C. Tran Zesheng Wan Wei Yao Liu Shahab Asgharzadeh Richard Sposto Hong Wei Wu Robert C. Seeger 《Cancer immunology, immunotherapy : CII》2013,62(10):1637-1648