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951.
Background
LZAP was isolated as a binding protein of the Cdk5 activator p35. LZAP has been highly conserved during evolution and has been shown to function as a tumor suppressor in various cancers. This study aimed to investigate LZAP expression and its prognostic value in hepatocellular carcinoma (HCC). Meanwhile, the function of LZAP in hepatocarcinogenesis was further investigated in cell culture models and mouse models.Methods
Real-time quantitative PCR, western blot and immunohistochemistry were used to explore LZAP expression in HCC cell lines and primary HCC clinical specimens. The functions of LZAP in the proliferation, colony formation, cell cycle, migration, invasion and apoptosis of HCC cell lines were also analyzed by infecting cells with an adenovirus containing full-length LZAP. The effect of LZAP on tumorigenicity in nude mice was also investigated.Results
LZAP expression was significantly decreased in the tumor tissues and HCC cell lines. Clinicopathological analysis showed that LZAP expression was significantly correlated with tumor size, histopathological classification and serum α-fetoprotein (AFP). The Kaplan–Meier survival curves revealed that decreasing LZAP expression was associated with poor prognosis in HCC patients. LZAP expression was an independent prognostic marker of overall HCC patient survival in a multivariate analysis. The re-introduction of LZAP expression in the HepG2 and sk-Hep1 HCC cell lines significantly inhibited proliferation and colony formation in the HCC cells and induced G1 phase arrest and apoptosis of the HCC cells in vitro. Restoring LZAP expression in the HCC cell lines also inhibited migration and invasion. In addition, experiments with a mouse model revealed that LZAP overexpression could suppress HCC tumorigenicity in vivo.Conclusions
Our data suggest that LZAP may play an important role in HCC progression and could be a potential molecular therapy target for HCC. 相似文献952.
953.
Cantarel BL Erickson AR VerBerkmoes NC Erickson BK Carey PA Pan C Shah M Mongodin EF Jansson JK Fraser-Liggett CM Hettich RL 《PloS one》2011,6(11):e27173
Accurate protein identification in large-scale proteomics experiments relies upon a detailed, accurate protein catalogue, which is derived from predictions of open reading frames based on genome sequence data. Integration of mass spectrometry-based proteomics data with computational proteome predictions from environmental metagenomic sequences has been challenging because of the variable overlap between proteomic datasets and corresponding short-read nucleotide sequence data. In this study, we have benchmarked several strategies for increasing microbial peptide spectral matching in metaproteomic datasets using protein predictions generated from matched metagenomic sequences from the same human fecal samples. Additionally, we investigated the impact of mass spectrometry-based filters (high mass accuracy, delta correlation), and de novo peptide sequencing on the number and robustness of peptide-spectrum assignments in these complex datasets. In summary, we find that high mass accuracy peptide measurements searched against non-assembled reads from DNA sequencing of the same samples significantly increased identifiable proteins without sacrificing accuracy. 相似文献
954.
Zhou JP Chen X Feng S Luo SD Pan YL Zhong L Ji P Wang ZR Ma S Li LL Wei YQ Yang SY 《PloS one》2011,6(12):e28930
Despite many evidences supporting the concept of "oncogene addiction" and many hypotheses rationalizing it, there is still a lack of detailed understanding to the precise molecular mechanism underlying oncogene addiction. In this account, we developed a mathematic model of epidermal growth factor receptor (EGFR) associated signaling network, which involves EGFR-driving proliferation/pro-survival signaling pathways Ras/extracellular-signal-regulated kinase (ERK) and phosphoinositol-3 kinase (PI3K)/AKT, and pro-apoptotic signaling pathway apoptosis signal-regulating kinase 1 (ASK1)/p38. In the setting of sustained EGFR activation, the simulation results show a persistent high level of proliferation/pro-survival effectors phospho-ERK and phospho-AKT, and a basal level of pro-apoptotic effector phospho-p38. The potential of p38 activation (apoptotic potential) due to the elevated level of reactive oxygen species (ROS) is largely suppressed by the negative crosstalk between PI3K/AKT and ASK1/p38 pathways. Upon acute EGFR inactivation, the survival signals decay rapidly, followed by a fast increase of the apoptotic signal due to the release of apoptotic potential. Overall, our systems biology modeling together with experimental validations reveals that inhibition of survival signals and concomitant release of apoptotic potential jointly contribute to the tumor cell death following the inhibition of addicted oncogene in EGFR addicted cancers. 相似文献
955.
Sun L Tan LJ Lei SF Chen XD Li X Pan R Yin F Liu QW Yan XF Papasian CJ Deng HW 《PloS one》2011,6(11):e27325
Objective
Femoral neck geometric parameters (FNGPs), such as periosteal diameter (W), cross-sectional area (CSA), cortical thickness (CT), buckling ratio (BR), and section modulus (Z), are highly genetically correlated with body lean mass. However, the specific SNPs/genes shared by these phenotypes are largely unknown.Methods
To identify the specific SNPs/genes shared between FNGPs and appendicular lean mass (ALM), we performed an initial bivariate genome-wide association study (GWAS) by scanning ∼690,000 SNPs in 1,627 unrelated Han Chinese adults (802 males and 825 females) and a follow-up replicate study in 2,286 unrelated US Caucasians.Results
We identified 13 interesting SNPs that may be important for both FNGPs and ALM. Two SNPs, rs681900 located in the HK2 (hexokinase 2) gene and rs11859916 in the UMOD (uromodulin) gene, were bivariately associated with FNGPs and ALM (p = 7.58×10−6 for ALM-BR and p = 2.93×10−6 for ALM-W, respectively). The associations were then replicated in Caucasians, with corresponding p values of 0.024 for rs681900 and 0.047 for rs11859916. Meta-analyses yielded combined p values of 3.05×10−6 and 2.31×10−6 for rs681900 and rs11859916, respectively. Our findings are consistent with previous biological studies that implicated HK2 and UMOD in both FNGPs and ALM. Our study also identified a group of 11 contiguous SNPs, which spanned a region of ∼130 kb, were bivariately associated with FNGPs and ALM, with p values ranging from 3.06×10−7 to 4.60×10−6 for ALM-BR. The region contained two neighboring miRNA coding genes, MIR873 (MicroRNA873) and MIR876 (MicroRNA876).Conclusion
Our study implicated HK2, UMOD, MIR873 and MIR876, as pleiotropic genes underlying variation of both FNGPs and ALM, thus suggesting their important functional roles in co-regulating both FNGPs and ALM. 相似文献956.
Cheng ZX Sun B Wang SJ Gao Y Zhang YM Zhou HX Jia G Wang YW Kong R Pan SH Xue DB Jiang HC Bai XW 《PloS one》2011,6(8):e23752
Background
Epithelial to mesenchymal transition (EMT) induced by hypoxia is one of the critical causes of treatment failure in different types of human cancers. NF-κB is closely involved in the progression of EMT. Compared with HIF-1α, the correlation between NF-κB and EMT during hypoxia has been less studied, and although the phenomenon was observed in the past, the molecular mechanisms involved remained unclear.Methodology/Principal Findings
Here, we report that hypoxia or overexpression of hypoxia-inducible factor-1α (HIF-1α) promotes EMT in pancreatic cancer cells. On molecular or pharmacologic inhibition of NF-κB, hypoxic cells regained expression of E-cadherin, lost expression of N-cadherin, and attenuated their highly invasive and drug-resistant phenotype. Introducing a pcDNA3.0/HIF-1α into pancreatic cancer cells under normoxic conditions heightened NF-κB activity, phenocopying EMT effects produced by hypoxia. Conversely, inhibiting the heightened NF-κB activity in this setting attenuated the EMT phenotype.Conclusions/Significance
These results suggest that hypoxia or overexpression of HIF-1α induces the EMT that is largely dependent on NF-κB in pancreatic cancer cells. 相似文献957.
958.
Rust secreted protein Ps87 is conserved in diverse fungal pathogens and contains a RXLR-like motif sufficient for translocation into plant cells 总被引:3,自引:0,他引:3
Background
Effector proteins of biotrophic plant pathogenic fungi and oomycetes are delivered into host cells and play important roles in both disease development and disease resistance response. How obligate fungal pathogen effectors enter host cells is poorly understood. The Ps87 gene of Puccinia striiformis encodes a protein that is conserved in diverse fungal pathogens. Ps87 homologs from a clade containing rust fungi are predicted to be secreted. The aim of this study is to test whether Ps87 may act as an effector during Puccinia striiformis infection.Methodology/Principal Findings
Yeast signal sequence trap assay showed that the rust protein Ps87 could be secreted from yeast cells, but a homolog from Magnaporthe oryzae that was not predicted to be secreted, could not. Cell re-entry and protein uptake assays showed that a region of Ps87 containing a conserved RXLR-like motif [K/R]RLTG was confirmed to be capable of delivering oomycete effector Avr1b into soybean leaf cells and carrying GFP into soybean root cells. Mutations in the Ps87 motif (KRLTG) abolished the protein translocation ability.Conclusions/Significance
The results suggest that Ps87 and its secreted homologs could utilize similar protein translocation machinery as those of oomycete and other fungal pathogens. Ps87 did not show direct suppression activity on plant defense responses. These results suggest Ps87 may represent an “emerging effector” that has recently acquired the ability to enter plant cells but has not yet acquired the ability to alter host physiology. 相似文献959.
Liang Y Yin D Hou L Zheng T Wang J Meng X Lu Z Song X Pan S Jiang H Liu L 《PloS one》2011,6(8):e23908
Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, was recently reported to inhibit proliferation of various cancer cells significantly. Here we try to determine the effect and mechanism of EF24 on hepatocellular carcinoma. 2 μM EF24 was found to inhibit the proliferation of PLC/PRF/5, Hep3B, HepG2, SK-HEP-1 and Huh 7 cell lines. However, even 8 μM EF24 treatment did not affect the proliferation of normal liver LO2 cells. Accordingly, 20 mg/kg/d EF24 inhibited the growth of the tumor xenografts conspicuously while causing no apparent change in liver, spleen or body weight. In addition, significant apoptosis and G(2)/M phase cell cycle arrest were found using flow cytometry. Besides, caspases and PARP activation and features typical of apoptosis including fragmented nuclei with condensed chromatin were also observed. Furthermore, the mechanism was targeted at the reduction of nuclear factor kappa b (NF-κB) pathway and the NF-κB-regulated gene products Bcl-2, COX-2, Cyclin B1. Our study has offered a strategy that EF24 being a therapeutic agent for hepatocellular carcinoma. 相似文献
960.
Quantitative real-time PCR (qPCR) is the gold standard for the quantification of specific nucleic acid sequences. However, a serious concern has been revealed in a recent report: supercoiled plasmid standards cause significant over-estimation in qPCR quantification. In this study, we investigated the effect of plasmid DNA conformation on the quantification of DNA and the efficiency of qPCR. Our results suggest that plasmid DNA conformation has significant impact on the accuracy of absolute quantification by qPCR. DNA standard curves shifted significantly among plasmid standards with different DNA conformations. Moreover, the choice of DNA measurement method and plasmid DNA conformation may also contribute to the measurement error of DNA standard curves. Due to the multiple effects of plasmid DNA conformation on the accuracy of qPCR, efforts should be made to assure the highest consistency of plasmid standards for qPCR. Thus, we suggest that the conformation, preparation, quantification, purification, handling, and storage of standard plasmid DNA should be described and defined in the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) to assure the reproducibility and accuracy of qPCR absolute quantification. 相似文献