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1.
SPHK1 (sphingosine kinase 1), a regulator of sphingolipid metabolites, plays a causal role in the development of hepatocellular carcinoma (HCC) through augmenting HCC invasion and metastasis. However, the mechanism by which SPHK1 signaling promotes invasion and metastasis in HCC remains to be clarified. Here, we reported that SPHK1 induced the epithelial-mesenchymal transition (EMT) by accelerating CDH1/E-cadherin lysosomal degradation and facilitating the invasion and metastasis of HepG2 cells. Initially, we found that SPHK1 promoted cell migration and invasion and induced the EMT process through decreasing the expression of CDH1, which is an epithelial marker. Furthermore, SPHK1 accelerated the lysosomal degradation of CDH1 to induce EMT, which depended on TRAF2 (TNF receptor associated factor 2)-mediated macroautophagy/autophagy activation. In addition, the inhibition of autophagy recovered CDH1 expression and reduced cell migration and invasion through delaying the degradation of CDH1 in SPHK1-overexpressing cells. Moreover, the overexpression of SPHK1 produced intracellular sphingosine-1-phosphate (S1P). In response to S1P stimulation, TRAF2 bound to BECN1/Beclin 1 and catalyzed the lysine 63-linked ubiquitination of BECN1 for triggering autophagy. The deletion of the RING domain of TRAF2 inhibited autophagy and the interaction of BECN1 and TRAF2. Our findings define a novel mechanism responsible for the regulation of the EMT via SPHK1-TRAF2-BECN1-CDH1 signal cascades in HCC cells. Our work indicates that the blockage of SPHK1 activity to attenuate autophagy may be a promising strategy for the prevention and treatment of HCC. 相似文献
2.
Bing Han Yujia Zheng Le Wang Haixu Wang Jiaxin Du Fanglei Ye Tongwen Sun Lianfeng Zhang 《Journal of cellular physiology》2019,234(11):20859-20868
Vascular invasion (VI) in hepatocellular carcinoma (HCC) is an important clinical parameter to predict survival. In this study, we collected microRNA (miRNA) expression data from HCC patients using The Cancer Genome Atlas database and identified a novel miRNA signature associated with VI. First, we categorized HCC patients into groups with or without VI (VI+ and VI−). We identified three miRNAs (miRNA-210, miRNA-10b, and miRNA-9-1) that were associated with VI according to a Kaplan–Meier analysis. This three-miRNA signature exhibited good predictive ability for VI in patients with HCC according to a receiver operating characteristic curve analysis at 1, 3, and 5 years. Patients with HCC with a high risk score exhibited a trend toward worse outcomes as determined by multivariable Cox regression and stratified analyses. This three-miRNA signature provides an accurate prediction of VI and can be used as an independent prognostic indicator for predicting VI in HCC patients. 相似文献
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《Current biology : CB》2020,30(7):1231-1244.e4
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Xian-Zheng Gao Guan-Nan Wang Wu-Gan Zhao Jing Han Chang-Ying Diao Xiao-Hui Wang Sheng-Lei Li Wen-Cai Li 《Journal of cellular physiology》2019,234(9):15035-15043
Hypoxia is a common biological hallmark of solid cancers, which has been proposed to be associated with oncogenesis and chemotherapy resistance. The purpose of the present study was to investigate the role and underlying mechanisms of olfactomedin 4 (OLFM4) in the hypoxia-induced invasion, epithelial–mesenchymal transition (EMT), and chemotherapy resistance of non-small-cell lung cancer (NSCLC). We observed dramatically upregulated expression of OLFM4 in several NSCLC cell lines, and this effect was more pronounced in A549 and H1299 cells. In addition, our data revealed that OLFM4 expression was remarkably increased in both A549 and H1299 cells under hypoxic microenvironment, accompanied by enhanced levels of hypoxia-inducible factor (HIF)-1α protein. The HIF-1α level was elevated in response to hypoxia, resulting in the regulation of OLFM4. Interestingly, OLFM4 was a positive regulator of hypoxia-driven HIF-1α production. Moreover, depletion of OLFM4 modulated multiple EMT-associated proteins, as evidenced by the enhanced E-cadherin levels along with the diminished expression of N-cadherin and vimentin in response to hypoxia, and thus blocked invasion ability of A549 and H1299 cells following exposure to hypoxia. Furthermore, ablation of OLFM4 accelerated the sensitivity of A549 cells to cisplatin under hypoxic conditions, implying that OLFM4 serves as a key regulator in chemotherapeutic resistance under hypoxia. In conclusion, OLFM4/HIF-1α axis might be a potential therapeutic strategy for NSCLC. 相似文献
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互花米草(Spartina alterniflora)的入侵给海岸带盐沼生态系统的结构和功能带来了显著影响。互花米草盐沼中的硫含量高于附近的土著芦苇(Phragmites australis)盐沼。为探讨硫元素对互花米草和芦苇竞争过程的可能影响及其作用机制,以50mmol·L–1的Na2SO4和Na2S对互花米草和芦苇进行处理,分析处理前后5天内两种植物光合气体交换和叶绿素荧光指标变化的差异,实验另设等Na+浓度的Na Cl处理作为比较。研究发现:Na2S对互花米草和芦苇光合作用影响的差异最大,Na Cl次之,Na2SO4最小。Na2S处理后,互花米草净光合速率(Pn)出现显著上升,芦苇Pn值大幅度下降。互花米草的光饱和点(Isat)上升而芦苇的Isat值无变化。表明Na2S处理对互花米草的光合能力有促进作用,但对芦苇的光合能力有抑制作用。Na Cl处理后互花米草Pn值也出现小幅上升,而芦苇Pn值略有下降。Na2SO4处理对互花米草和芦苇的Pn值均无显著影响。除Na2SO4处理的互花米草外,不同盐处理后的互花米草和芦苇非光化学淬灭(NPQ)均出现上升趋势。研究结果表明互花米草对环境硫胁迫的适应能力显著高于芦苇,暗示盐沼高硫环境尤其是硫化物有助于互花米草相对于芦苇的竞争,也很可能是其形成单一植被的重要原因之一。 相似文献
8.
Infiltration of a facultative ant–plant mutualism by the introduced Argentine ant: effects on mutualist diversity and mutualism benefits 下载免费PDF全文
1. Ant–plant mutualisms have been the focus of considerable empirical research, but few studies have investigated how introduced ants affect these interactions. Using 2 years of survey data, this study examines how the introduced Argentine ant [Linepithema humile (Mayr)] differs from native ants with respect to its ability to protect the extrafloral nectary‐bearing coast barrel cactus (Ferocactus viridescens) in Southern California. 2. Eighteen native ant species visited cacti in uninvaded areas, but cacti in invaded areas were primarily visited by the Argentine ant. The main herbivore of the coast barrel cactus present at the study sites is a leaf‐footed bug (Narnia wilsoni). 3. Herbivore presence (the fraction of surveys in which leaf‐footed bugs were present on individual cacti) was negatively related to ant presence (the fraction of surveys in which ants were present on individual cacti). Compared with cacti in uninvaded areas, those in invaded areas were less likely to have herbivores and when they did had them less often. 4. Seed mass was negatively related to herbivore presence, and this relationship did not differ for cacti in invaded areas versus those in uninvaded areas. 5. Although the Argentine ant might provide superior protection from herbivores, invasion‐induced reductions in ant mutualist diversity could potentially compromise plant reproduction. The cumulative number of ant species on individual cacti over time was lower in invaded areas and was associated with a shortened seasonal duration of ant protection and reduced seed mass. These results support the hypothesis that multiple partners may enhance mutualism benefits. 相似文献
9.
pKa predictions for proteins,RNAs, and DNAs with the Gaussian dielectric function using DelPhi pKa 下载免费PDF全文
We developed a Poisson‐Boltzmann based approach to calculate the values of protein ionizable residues (Glu, Asp, His, Lys and Arg), nucleotides of RNA and single stranded DNA. Two novel features were utilized: the dielectric properties of the macromolecules and water phase were modeled via the smooth Gaussian‐based dielectric function in DelPhi and the corresponding electrostatic energies were calculated without defining the molecular surface. We tested the algorithm by calculating values for more than 300 residues from 32 proteins from the PPD dataset and achieved an overall RMSD of 0.77. Particularly, the RMSD of 0.55 was achieved for surface residues, while the RMSD of 1.1 for buried residues. The approach was also found capable of capturing the large shifts of various single point mutations in staphylococcal nuclease (SNase) from ‐cooperative dataset, resulting in an overall RMSD of 1.6 for this set of pKa's. Investigations showed that predictions for most of buried mutant residues of SNase could be improved by using higher dielectric constant values. Furthermore, an option to generate different hydrogen positions also improves predictions for buried carboxyl residues. Finally, the calculations on two RNAs demonstrated the capability of this approach for other types of biomolecules. Proteins 2015; 83:2186–2197. © 2015 Wiley Periodicals, Inc. 相似文献
10.
Eric Lombaert Thomas Guillemaud Jonathan Lundgren Robert Koch Benoît Facon Audrey Grez Antoon Loomans Thibaut Malausa Oldrich Nedved Emma Rhule Arnstein Staverlokk Tove Steenberg Arnaud Estoup 《Molecular ecology》2014,23(24):5979-5997
Inferences about introduction histories of invasive species remain challenging because of the stochastic demographic processes involved. Approximate Bayesian computation (ABC) can help to overcome these problems, but such method requires a prior understanding of population structure over the study area, necessitating the use of alternative methods and an intense sampling design. In this study, we made inferences about the worldwide invasion history of the ladybird Harmonia axyridis by various population genetics statistical methods, using a large set of sampling sites distributed over most of the species’ native and invaded areas. We evaluated the complementarity of the statistical methods and the consequences of using different sets of site samples for ABC inferences. We found that the H. axyridis invasion has involved two bridgehead invasive populations in North America, which have served as the source populations for at least six independent introductions into other continents. We also identified several situations of genetic admixture between differentiated sources. Our results highlight the importance of coupling ABC methods with more traditional statistical approaches. We found that the choice of site samples could affect the conclusions of ABC analyses comparing possible scenarios. Approaches involving independent ABC analyses on several sample sets constitute a sensible solution, complementary to standard quality controls based on the analysis of pseudo‐observed data sets, to minimize erroneous conclusions. This study provides biologists without expertise in this area with detailed methodological and conceptual guidelines for making inferences about invasion routes when dealing with a large number of sampling sites and complex population genetic structures. 相似文献