Methylation of EZH2 by PRMT1 regulates its stability and promotes breast cancer metastasis

Enhancer of zeste homolog 2 (EZH2), a key histone methyltransferase and EMT inducer, is overexpressed in diverse carcinomas, including breast cancer. However, the molecular mechanisms of EZH2 dysregulation in cancers are still largely unknown. Here, we discover that EZH2 is asymmetrically dimethylated at R342 (meR342-EZH2) by PRMT1. meR342-EZH2 was found to inhibit the CDK1-mediated phosphorylation of EZH2 at T345 and T487, thereby attenuating EZH2 ubiquitylation mediated by the E3 ligase TRAF6. We also demonstrate that meR342-EZH2 resulted in a decrease in EZH2 target gene expression, but an increase in breast cancer cell EMT, invasion and metastasis. Moreover, we confirm the positive correlations among PRMT1, meR342-EZH2 and EZH2 expression in the breast cancer tissues. Finally, we report that high expression levels of meR342-EZH2 predict a poor clinical outcome in breast cancer patients. Our findings may provide a novel diagnostic target and promising therapeutic target for breast cancer metastasis.Subject terms: Metastasis, Tumour biomarkers, Ubiquitylation, Gene regulation     

Identification of blood biomarkers of rheumatoid arthritis by transcript profiling of peripheral blood mononuclear cells from the rat collagen-induced arthritis model

Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease that results in joint destruction and subsequent loss of function. To better understand its pathogenesis and to facilitate the search for novel RA therapeutics, we profiled the rat model of collagen-induced arthritis (CIA) to discover and characterize blood biomarkers for RA. Peripheral blood mononuclear cells (PBMCs) were purified using a Ficoll gradient at various time points after type II collagen immunization for RNA preparation. Total RNA was processed for a microarray analysis using Affymetrix GeneChip technology. Statistical comparison analyses identified differentially expressed genes that distinguished CIA from control rats. Clustering analyses indicated that gene expression patterns correlated with laboratory indices of disease progression. A set of 28 probe sets showed significant differences in expression between blood from arthritic rats and that from controls at the earliest time after induction, and the difference persisted for the entire time course. Gene Ontology comparison of the present study with previous published murine microarray studies showed conserved Biological Processes during disease induction between the local joint and PBMC responses. Genes known to be involved in autoimmune response and arthritis, such as those encoding Galectin-3, Versican, and Socs3, were identified and validated by quantitative TaqMan RT-PCR analysis using independent blood samples. Finally, immunoblot analysis confirmed that Galectin-3 was secreted over time in plasma as well as in supernatant of cultured tissue synoviocytes of the arthritic rats, which is consistent with disease progression. Our data indicate that gene expression in PBMCs from the CIA model can be utilized to identify candidate blood biomarkers for RA.     

Migration timing influences the responses of birds to food shortage at their refuelling site

Because migration is highly time‐constrained and migration timing varies among individuals, the responses of migrants to food shortage at a refuelling site could differ between individuals that arrive early and late at the site. To test this hypothesis, we compared the stopover decision, in terms of occurrence and length of stay (LOS), of radiotagged Great Knots Calidris tenuirostris before (2012) and after (2015) a dramatic decline in food supply at a critical spring final pre‐breeding refuelling site in the northern Yellow Sea. The probability of occurrence at the refuelling site was consistent between the two years, whereas the average LOS significantly shortened in the year of food shortage in late‐arriving individuals. This suggests migration timing intensifies the influence of food shortage in late‐arriving individuals, which might be more sensitive and vulnerable to food shortage at refuelling sites compared with early‐arriving individuals.     

PTEN基因通过调控ROS抑制结肠癌细胞增殖

为了探讨PTEN基因在结肠癌中的作用以及其机制研究,MTT法检测结肠癌细胞细胞增殖;蛋白免疫印迹检测结肠癌细胞中Ki67蛋白的表达;DCFDA染色流式细胞仪检测结肠癌细胞中ROS水平。结果表明PTEN基因能明显抑制结肠癌细胞细胞增殖;PTEN基因能显著降低结肠癌细胞中Ki67蛋白的表达;细胞内ROS水平在PTEN基因处理组中明显高于空质粒结肠癌细胞组;NAC预处理可明显抑制PTEN基因抑制的细胞增殖;NAC预处理可显著抑制PTEN基因对结肠癌细胞Ki67蛋白的降低作用。PTEN基因能够抑制结肠癌细胞增殖并上调结肠癌细胞内ROS水平。     

Maikottia属骨骼微细构造及其分类

Ｍａｉｋｏｔｔｉａ Ｌａｕｒｕｓｅｖｉｃｈ,１９６７属是泡沫珊瑚目中较特殊的类型,呈多角块状复体。经电镜研究表明,其骨骼微细构造以晶片型层状骨骼为主,隔壁刺由复式杆晶榍组成,层状骨骼包绕隔壁刺,在隔壁刺内包绕和联结单杆晶榍。体壁和横板均由层状骨骼组成。本属的纤状骨骼属较原始简单类型－晶粒和短轴晶柱,它组成复式杆晶榍内单杆晶榍的轴带,并呈分散状排列。根据该属为泡沫珊瑚类型隔壁及复式杆晶榍,将其归入泡     

Molecular engineering of respiratory syncytial virus immunogen for rational redesign of prophylactic peptide vaccines against pediatric viral pneumonia

The immunogen FFL_001 of respiratory syncytial virus (RSV), a widely spread virus that infects the lungs and breathing passages, is a three-helix bundle protein of 115 amino acids long that consists of three helical arms H1, H2 and H3. Here, we attempted to perform molecular engineering of the immunogen, aiming to considerably reduce the protein scaffold of FFL_001 with only moderate activity loss. Structural analysis and molecular dynamics (MD) simulations revealed that two helices H2 and H3 of the FFL_001 three-helix bundle can directly interact with its cognate monoclonal antibody Motavizumab, while the remaining helix H1 plays a crucial role in stabilisation of the three-helix bundle conformation. Binding of the two split peptide segments separately representing FFL_001 two-helix bundle H2-H3 and Motavizumab-binding site to the antibody would incur considerable entropy penalty as compared to binding of the intact FFL_001, suggesting that peptide segments are highly flexible that exhibit a strong intrinsic disorder in solution. In this respect, a scheme was proposed to rationally redesign the immunogen protein scaffold by truncation and cyclisation of the three-helix bundle. The cyclisation was conducted on the spatially vicinal residue pairs in H2 and H3 helical arms by mutating the residue to cysteine and introducing a disulphide bond across them. Consequently, we obtained three cyclic peptides that were theoretically predicted to have strong binding potency towards Motavizumab. In order to substantiate the computational finding, binding affinity of the designed cyclic peptide and its linear counterpart was determined. Consistently, no binding can be found between the linear peptide and Motavizumab (K_d = n.d.), while a moderately high affinity was observed for cyclic peptide (K_d = 16.2 nM).