The macrophage, one of the several key immune cell types, is believed to be involved in tumorigenesis. However, the mechanism of macrophages promoting tumor progression is largely unknown. The differentially secreted proteins of M1 and M2 macrophages were analyzed by mass spectrometry. We performed GST pull-down assay for the identification of cell-membrane receptors that interact with chitinase 3-like protein 1 (CHI3L1) protein. The mouse model was used to validate the function of CHI3L1 in cancer metastasis in vivo. Protein phosphorylation and gene expression were performed to study the signaling pathway activation of cancer cells after CHI3L1 treatment. M2 macrophage-secreted CHI3L1 promoted the metastasis of gastric and breast cancer cells in vitro and in vivo. The CHI3L1 protein functioned by interacting with interleukin-13 receptor α2 chain (IL-13Rα2) molecules on the plasma membranes of cancer cells. Activation of IL-13Rα2 by CHI3L1 triggered the activation of the mitogen-activated protein kinase signaling pathway, leading to the upregulated expression of matrix metalloproteinase genes, which promoted tumor metastasis. The results of this study indicated that the level of CHI3L1 protein in the sera of patients with gastric or breast cancer was significantly elevated compared with those of healthy donors. Our study revealed a novel aspect of macrophages with respect to cancer metastasis and showed that CHI3L1 could be a marker of metastatic gastric and breast cancer in patients.

Background: MicroRNAs (miRNAs) are key posttranscriptional regulators of gene expression that are implicated in many processes of eukaryotic cells. It is known that the expression profiles of host miRNAs can be reshaped by viruses. However, a systematic investigation of marine invertebrate miRNAs that respond to virus infection has not yet been performed. Results: In this study, the shrimp Marsupenaeus japonicus was challenged by white spot syndrome virus (WSSV). Small RNA sequencing of WSSV-infected shrimp at different time post-infection (0, 6, 24 and 48 h) identified 63 host miRNAs, 48 of which were conserved in other animals, representing 43 distinct families. Of the identified host miRNAs, 31 were differentially expressed in response to virus infection, of which 25 were up-regulated and six down-regulated. The results were confirmed by northern blots. The TargetScan and miRanda algorithms showed that most target genes of the differentially expressed miRNAs were related to immune responses. Gene ontology analysis revealed that immune signaling pathways were mediated by these miRNAs. Evolutionary analysis showed that three of them, miR-1, miR-7 and miR-34, are highly conserved in shrimp, fruit fly and humans and function in the similar pathways. Conclusions: Our study provides the first large-scale characterization of marine invertebrate miRNAs that respond to virus infection. This will help to reveal the molecular events involved in virus-host interactions mediated by miRNAs and their evolution in animals.

Viruses are believed to be responsible for the mortality of host organisms. However, some recent investigations reveal that viruses may be essential for host survival. To date, it remains unclear whether viruses are beneficial or harmful to their hosts. To reveal the roles of viruses in the virus-host interactions, viromes and microbiomes of sediment samples from three deep-sea hydrothermal vents were explored in this study. To exclude the influence of exogenous DNAs on viromes, the virus particles were purified with nuclease (DNase I and RNase A) treatments and cesium chloride density gradient centrifugation. The metagenomic analysis of viromes without exogenous DNA contamination and microbiomes of vent samples indicated that viruses had compensation effects on the metabolisms of their host microorganisms. Viral genes not only participated in most of the microbial metabolic pathways but also formed branched pathways in microbial metabolisms, including pyrimidine metabolism; alanine, aspartate, and glutamate metabolism; nitrogen metabolism and assimilation pathways of the two-component system; selenocompound metabolism; aminoacyl-tRNA biosynthesis; and amino sugar and nucleotide sugar metabolism. As is well known, deep-sea hydrothermal vent ecosystems exist in relatively isolated environments which are barely influenced by other ecosystems. The metabolic compensation of hosts mediated by viruses might represent a very important aspect of virus-host interactions. IMPORTANCE Viruses are the most abundant biological entities in the oceans and have very important roles in regulating microbial community structure and biogeochemical cycles. The relationship between virus and host microbes is broadly thought to be that of predator and prey. Viruses can lyse host cells to control microbial population sizes and affect community structures of hosts by killing specific microbes. However, viruses also influence their hosts through manipulation of bacterial metabolism. We found that viral genes not only participated in most microbial metabolic pathways but also formed branched pathways in microbial metabolisms. The metabolic compensation of hosts mediated by viruses may help hosts to adapt to extreme environments and may be essential for host survival.

Growing evidence from mammals suggests that host microRNAs (miRNAs) play important roles in the antiviral immune response. However, the roles of invertebrate miRNAs in response to virus infection remain to be investigated. Based on our previous studies, the shrimp miR-7 was found to be upregulated in response to white spot syndrome virus (WSSV) infection. In this study, the results showed that shrimp miR-7 could target the 3′-untranslated region (3′UTR) of the WSSV early gene wsv477, implying that miR-7 was involved in viral DNA replication. In insect High Five cells, the synthesized miR-7 significantly decreased the expression level of the fluorescent construct bearing the 3′UTR of wsv477 compared with the expression of the control constructs. When the activity of transfected miR-7 was blocked by locked-nucleic-acid (LNA)-modified anti-miR-7 oligonucleotide (AMO-miR-7), the repression of luciferase gene expression by miR-7 was relieved. In vivo , when the synthesized miR-7 was injected into shrimp, the numbers of WSSV genome copies/mg gills were 1,000-fold lower than those of WSSV only at 72 and 96 h postinfection. The results indicated that the blocking of endogenous miR-7 by AMO-miR-7 led to about a 10-fold increase of WSSV genome copies/mg gills in WSSV-infected shrimp compared with the control WSSV only. Further, it was revealed that the host Dicer1 was an important component for the biogenesis of miR-7, which had a large effect on virus infection. Therefore, our study revealed a novel regulatory function for an invertebrate miRNA in host-virus interactions by targeting the viral early gene.

The innate immune system, including the cell-based immunity (mainly apoptosis and phagocytosis) and the humoral immunity (such as pro-phenoloxidase system), is the first defense line of animals against the infection of pathogens in a non-specific manner, which is fine regulated through the gene expression regulations. The microRNAs (miRNAs) are recognized as important regulators of gene expression. To date, however, a comprehensive view about the regulation of innate immunity by miRNAs is not available. To address this issue, the signature miRNAs involved in the innate immunity were characterized in this study. The phagocytosis, apoptosis and phenoloxidase (PO), a key enzyme in the pro-phenoloxidase system, of invertebrate shrimp were activated or inhibited, followed by the small RNA sequencing. The results showed that a total of 24 miRNAs took great effects on phagocytosis, apoptosis or the pro-phenoloxidase system, which were further confirmed by Northern blots. Among the 24 innate immunity-associated miRNAs, 21 miRNAs were conserved in animals, suggesting that these miRNAs might share the similar or the same functions in different species of animals. Based on degradome sequencing and prediction of target genes, it was found that the miRNAs might mediate the regulations of phagocytosis, apoptosis or pro-phenoloxidase system by targeting different genes. Therefore our study presented the first comprehensive view of the miRNAs associated with innate immunity, which would facilitate to reveal the molecular events in the regulation of innate immunity.