BackgroundOrf is a zoonotic and epitheliotrophic contagious disease that mainly affects sheep, goats, wild ruminants, and humans with a worldwide distribution. To date, there is little information on the characterization of ORFV strains that are endemic in Mainland China. In addition, the relationship between the severity of disease and the molecular profile of ORFV strains has not been fully elucidated.ResultsFrom the recent outbreak of a sheep herd in Nongan, northeast of China, the novel orf virus (ORFV) strain NA1/11 was successfully isolated. Western blot analysis indicated that the NA1/11 strain cross reacts with monoclonal antibody A3 and infected sheep ORFV antiserum. The purified virions revealed the typical ovoid shape when observed by atomic force microscopy. To determine the genetic characteristics of the NA1/11 strain, the sequences of ORFV011 (B2L), ORFV059 (F1L), ORFV109, ORFV110 and ORFv132 (VEGF) genes were amplified and compared with reference parapoxvirus strains. Non-metric multidimensional scaling (nMDS) was performed to analyze the nucleotide similarities between different ORFV strains.ConclusionsPhylogenetic analysis based on ORFV 011 nucleotide sequences showed that the NA1/11strain was closely related to Xinjiang and Gansu strains. ORFV110 and ORFV132 genes are highly variable. The results revealed that precise phylogenetic analysis might provide evidence for genetic variation and movement of circulating ORFV strains in Northeast China. In addition, nMDS analysis showed that geographic isolation and animal host are likely major factors resulting in genetic differences between ORFV strains.

BackgroundRobust and precise molecular prognostic predictors for luminal breast cancer are required. This study aimed to identify key methylation sites in luminal breast cancer, as well as precise molecular tools for predicting prognosis.MethodsWe compared methylation levels of normal and luminal breast cancer samples from The Cancer Genome Atlas dataset. The relationships among differentially methylated sites, corresponding mRNA expression levels and prognosis were further analysed. Differentially expressed genes in normal and cancerous samples were analysed, followed by the identification of prognostic signature genes. Samples were divided into low- and high-risk groups based on the signature genes. Prognoses of low- and high-risk groups were compared. The Gene Expression Omnibus dataset were used to validate signature genes for prognosis prediction. Prognosis of low- and high-risk groups in Luminal A and Luminal B samples from the TCGA and the Metabric cohort dataset were analyzed. We also analysed the correlation between clinical features of low- and high- risk groups as well as their differences in gene expression.ResultsFourteen methylation sites were considered to be related to luminal breast cancer prognosis because their methylation levels, mRNA expression and prognoses were closely related to each other. The methylation level of SOSTDC1 was used to divide samples into hypo- and hyper-methylation groups. We also identified an mRNA signature, comprising eight transcripts, ESCO2, PACSIN1, CDCA2, PIGR, PTN, RGMA, KLK4 and CENPA, which was used to divide samples into low- and high-risk groups. The low-risk group showed significantly better prognosis than the high-risk group. A correlation analysis revealed that the risk score was an independent prognostic factor. Low- and high- risk groups significantly correlated with the survival ratio in Luminal A samples, but not in Luminal B samples on the basis of the TCGA and the Metabric cohort dataset. Further functional annotation demonstrated that the differentially expressed genes were mainly involved in cell cycle and cancer progression.ConclusionsWe identified several key methylation sites and an mRNA signature for predicting luminal breast cancer prognosis. The signature exhibited effective and precise prediction of prognosis and may serve as a prognostic and diagnostic marker for luminal breast cancer.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4314-9) contains supplementary material, which is available to authorized users.

The translationally controlled tumor protein (TCTP) can be secreted independently of the endoplasmic reticulum/Golgi pathway and has extrinsic activities when it is characterized as the histamine releasing factor (HRF). Despite its important role in allergies and inflammation, little is known about how extracellular TCTP affects cancer progression. In this study, we found that TCTP was overexpressed in the interstitial tissue of colorectal cancer (CRC) and its expression correlated with poor survival, high pathological grades and metastatic TNM stage in CRC patients. TCTP expression was greater in metastatic liver tissue than in primary tumors and was increased in highly invasive CRC cells. We demonstrated that the expression of TCTP was regulated by HIF-1α and its release was increased in response to low serum and hypoxic stress. Recombinant human TCTP (rhTCTP) promoted the migration and invasiveness of CRC cells in vitro and contributed to distant liver metastasis in vivo. Furthermore, rhTCTP activated Cdc42, phosphorylated JNK (p-JNK), increasing the translocation of p-JNK from the cytoplasm to the nucleus, as well as the secretion of MMP9. In addition, the expression of TCTP positively correlated with that of Cdc42 and p-JNK in clinical CRC samples. The silencing of Cdc42, JNK and MMP9 significantly inhibited the Matrigel invasion of rhTCTP-enhanced CRC cells. Collectively, these results identify a new role for extracellular TCTP as a promoter of CRC progression and liver metastases via Cdc42/JNK/MMP9 activation.

Orf virus (ORFV), a species of the genus Parapoxvirus of the family Poxviridae, causes non-systemic, highly contagious, and eruptive disease in sheep, goat, and other wild and domestic ruminants. Our previous work shows orf to be ubiquitous in the Fujian Province of China, a region where there is considerable heterogeneity among ORFVs. In this study, we sequenced full genomes of four Fujian goat ORFV strains (OV-GO, OV-YX, OV-NP, and OV-SJ1). The four strains were 132–139 kb in length, with each containing 124–132 genes and about 64% G+C content. The most notable differences between the four strains were found near the genome termini. OV-NP lacked seven and OV-SJ1 lacked three genes near the right terminus when compared against other ORFVs. We also investigated the skin-virulence of the four Fujian ORFVs in goats. The ORFVs with gene deletions showed low virulence while the ORFVs without gene deletions showed high virulence in goats suggesting gene deletion possibly leads to attenuation of ORFVs. Gene 134 was disrupted in OV-NP genome due to the lack of initial code. The phylogenetic tree based on complete Parapoxviruse genomes showed that sheep originated and goat originated ORFVs formed distinctly separate branches with 100% bootstrap. Based on the single gene phylogenetic tree of 132 genes of ORFVs, 47 genes can be easily distinguished as having originated from sheep or goats. In order to further reveal genetic variation presented in goat ORFVs and sheep ORFVs, we analyzed the deduced amino acid sequences of gene 008, multiple alignment of amino acid sequences of gene 008 from the genome of five goat ORFVs and four sheep ORFVs revealed 33 unique amino acids differentiating it as having sheep or goats as host. The availability of genomic sequences of four Fujian goat ORFVs aids in our understanding of the diversity of orf virus isolates in this region and can assist in distinguishing between orf strains that originate in sheep and goats.

No abstract