Background Runt-related transcription factor 1 (RUNX1) plays the roles of an oncogene and an anti-oncogene in epithelial tumours, and abnormally elevated RUNX1 has been suggested to contribute to the carcinogenesis of colorectal cancer (CRC). However, the mechanism remains unclear. Methods The expression of RUNX1 in CRC and normal tissues was detected by real-time quantitative PCR and Western blotting. The effect of RUNX1 on CRC migration and invasion was conducted by functional experiments in vitro and in vivo. Chromatin Immunoprecipitation assay verified the direct regulation of RUNX1 on the promoter of the KIT, which leads to the activation of Wnt/β-catenin signaling. Results RUNX1 expression is upregulated in CRC tissues. Upregulated RUNX1 promotes cell metastasis and epithelial to mesenchymal transition (EMT) of CRC both in vitro and in vivo. Furthermore, RUNX1 can activate Wnt/β-catenin signalling in CRC cells by directly interacting with β-catenin and targeting the promoter and enhancer regions of KIT to promote KIT transcription. These observations demonstrate that RUNX1 upregulation is a common event in CRC specimens and is closely correlated with cancer metastasis and that RUNX1 promotes EMT of CRC cells by activating Wnt/β-catenin signalling. Moreover, RUNX1 is regulated by Wnt/β-catenin. Conclusion Our findings first demonstrate that RUNX1 promotes CRC metastasis by activating the Wnt/β-catenin signalling pathway and EMT. Electronic supplementary material The online version of this article (10.1186/s13046-019-1330-9) contains supplementary material, which is available to authorized users.

BackgroundViral hemorrhagic fevers (VHFs) are a group of animal and human illnesses that are mostly caused by several distinct families of viruses including bunyaviruses, flaviviruses, filoviruses and arenaviruses. Although specific signs and symptoms vary by the type of VHF, initial signs and symptoms are very similar. Therefore rapid immunologic and molecular tools for differential diagnosis of hemorrhagic fever viruses (HFVs) are important for effective case management and control of the spread of VHFs. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assay is one of the reliable and desirable methods for specific detection and quantification of virus load. Multiplex PCR assay has the potential to produce considerable savings in time and resources in the laboratory detection.ResultsPrimers/probe sets were designed based on appropriate specific genes for each of 28 HFVs which nearly covered all the HFVs, and identified with good specificity and sensitivity using monoplex assays. Seven groups of multiplex one-step real-time qRT-PCR assays in a universal experimental system were then developed by combining all primers/probe sets into 4-plex reactions and evaluated with serial dilutions of synthesized viral RNAs. For all the multiplex assays, no cross-reactivity with other HFVs was observed, and the limits of detection were mainly between 45 and 150 copies/PCR. The reproducibility was satisfactory, since the coefficient of variation of Ct values were all less than 5% in each dilution of synthesized viral RNAs for both intra-assays and inter-assays. Evaluation of the method with available clinical serum samples collected from HFRS patients, SFTS patients and Dengue fever patients showed high sensitivity and specificity of the related multiplex assays on the clinical specimens.ConclusionsOverall, the comprehensive multiplex one-step real-time qRT-PCR assays were established in this study, and proved to be specific, sensitive, stable and easy to serve as a useful tool for rapid detection of HFVs.

Background: Crosstalk between cancer cells and tumor-associated macrophages (TAMs) mediates tumor progression in colorectal cancer (CRC). Cytoplasmic polyadenylation element binding protein 3 (CPEB3) has been shown to exhibit tumor-suppressive role in CRC. Methods: The expression of CPEB3, CD68, CD86 and CD163 was determined in CRC tissues. SW480 or HCT116 cells overexpressing CPEB3 and LoVo or RKO cells with CPEB3 knockdown were constructed. Stably transfected CRC cells were co-cultured with THP-1 macrophages to determine the malignant phenotype of CRC cells, macrophage polarization, and secretory signals. The inhibition of CPEB3 on tumor progression and M2-like TAM polarization was confirmed in nude mice. Results: Decreased CPEB3 expression in CRC was associated with fewer CD86 + TAMs and more CD163 + TAMs. CPEB3 knockdown in CRC cells increased the number of CD163 + TAMs and the expression of IL1RA, IL-6, IL-4 and IL-10 in TAM supernatants. TAMs enhanced CRC cell proliferation and invasion via IL-6, and then activated the IL-6R/STAT3 pathway in CRC cells. However, CPEB3 reduced the IL-6R protein levels by directly binding to IL-6R mRNA, leading to decreased phosphorylated-STAT3 expression in CRC cells. CCL2 was significantly increased in CPEB3 knockdown cells, while CCL2 antibody treatment rescued the effect of CPEB3 knockdown in promoting CD163 + TAM polarization. Eventually, we confirmed that CPEB3 inhibits tumor progression and M2-like TAM polarization in vivo. Conclusions: CPEB3 is involved in the crosstalk between CRC cells and TAMs by targeting IL-6R/STAT3 signaling.

Background: Crosstalk between cancer cells and tumor-associated macrophages (TAMs) mediates tumor progression in colorectal cancer (CRC). Cytoplasmic polyadenylation element binding protein 3 (CPEB3) has been shown to exhibit tumor-suppressive role in CRC. Methods: The expression of CPEB3, CD68, CD86 and CD163 was determined in CRC tissues. SW480 or HCT116 cells overexpressing CPEB3 and LoVo or RKO cells with CPEB3 knockdown were constructed. Stably transfected CRC cells were co-cultured with THP-1 macrophages to determine the malignant phenotype of CRC cells, macrophage polarization, and secretory signals. The inhibition of CPEB3 on tumor progression and M2-like TAM polarization was confirmed in nude mice. Results: Decreased CPEB3 expression in CRC was associated with fewer CD86+ TAMs and more CD163+ TAMs. CPEB3 knockdown in CRC cells increased the number of CD163+ TAMs and the expression of IL1RA, IL-6, IL-4 and IL-10 in TAM supernatants. TAMs enhanced CRC cell proliferation and invasion via IL-6, and then activated the IL-6R/STAT3 pathway in CRC cells. However, CPEB3 reduced the IL-6R protein levels by directly binding to IL-6R mRNA, leading to decreased phosphorylated-STAT3 expression in CRC cells. CCL2 was significantly increased in CPEB3 knockdown cells, while CCL2 antibody treatment rescued the effect of CPEB3 knockdown in promoting CD163+ TAM polarization. Eventually, we confirmed that CPEB3 inhibits tumor progression and M2-like TAM polarization in vivo. Conclusions: CPEB3 is involved in the crosstalk between CRC cells and TAMs by targeting IL-6R/STAT3 signaling.

Polyester fabrics were preirradiated by electron beam in air and then grafted by acrylic acid (AA) without excluding oxygen. Effects of preirradiation dose, monomer concentration, reaction temperature, storage time, sulfuric acid, and Mohr's salt were investigated in detail and are discussed. The results suggest that it is practicable and effective to graft AA onto polyester fabrics by means of the preirradiation method. FTIR and SEM were used to characterize AA-grafted polyester fabrics. A new band appearing at 1546 cm Ϫ1 in the FTIR spectrum implies that AA was indeed introduced onto PET macromolecules. Changes of the diameter and the surface structure of fabric fibers presented in SEM micrographs make it clear that a layer of grafted poly(acrylic acid) was formed on the surface of these PET fibers.

D-type cyclin (cyclin D, CYCD), combined with cyclin-dependent kinases (CDKs), participates in the regulation of cell cycle G1/S transition and plays an important role in cell division and proliferation. CYCD could affect the growth and development of herbaceous plants, such as Arabidopsis thaliana, by regulating the cell cycle process. However, its research in wood plants (e.g., poplar) is poor. Phylogenetic analysis showed that in Populus trichocarpa, CYCD3 genes expanded to six members, namely PtCYCD3;1–6. P. tomentosa CYCD3 genes were amplified based on the CDS region of P. trichocarpa CYCD3 genes. PtoCYCD3;3 showed the highest expression in the shoot tip, and the higher expression in young leaves among all members. Therefore, this gene was selected for further study. The overexpression of PtoCYCD3;3 in plants demonstrated obvious morphological changes during the observation period. The leaves became enlarged and wrinkled, the stems thickened and elongated, and multiple branches were formed by the plants. Anatomical study showed that in addition to promoting the differentiation of cambium tissues and the expansion of stem vessel cells, PtoCYCD3;3 facilitated the division of leaf adaxial epidermal cells and palisade tissue cells. Yeast two-hybrid experiment exhibited that 12 PtoCDK proteins could interact with PtoCYCD3;3, of which the strongest interaction strength was PtoCDKE;2, whereas the weakest was PtoCDKG;3. Molecular docking experiments further verified the force strength of PtoCDKE;2 and PtoCDKG;3 with PtoCYCD3;3. In summary, these results indicated that the overexpression of PtoCYCD3;3 significantly promoted the vegetative growth of Populus, and PtoCYCD3;3 may interact with different types of CDK proteins to regulate cell cycle processes.

Background: MiR-452-5p plays an essential role in the development of a variety of tumors, but little is known about its biological function and mechanism in colorectal cancer (CRC). Methods: The expression levels of miR-452-5p in CRC tissues and cells were detected by real-time quantitative PCR (qRT-PCR). Besides, the biological effects of miR-452-5p on CRC were investigated by functional experiments in vitro and in vivo . Furthermore, bioinformatics analysis, dual-luciferase reporter assay, chromatin immunecipitation assay, western blotting and recovery experiments were implemented to investigate the underlying molecular mechanism. Results: The expression level of miR-452-5p was up-regulated in CRC tissues. MiR-452-5p promoted CRC cell proliferation, cell cycle transition and chemoresistance, and inhibited cell apoptosis. Moreover, miR-452-5p directly targeted PKN2 and DUSP6 and subsequently activated the ERK/MAPK signaling pathway, and it was transcriptionally regulated by c-Jun. Conclusion: To conclude, miR-452-5p expression is up-regulated in CRC, which promotes the progression of CRC by activating the miR-452-5p—PKN2/DUSP6—c-Jun positive feedback loop. These findings indicate that miR-452-5p may act as a potential therapeutic target and clinical response biomarker for CRC.

DDX39B is a member of the DEAD box (DDX) RNA helicase family required for nearly all cellular RNA metabolic processes. The exact role and potential molecular mechanism of DDX39B in the progression of human colorectal cancer (CRC) remain to be investigated. In the present study, we demonstrate that DDX39B expression is higher in CRC tissues than in adjacent normal tissues. Gain- and loss-of-function assays revealed that DDX39B facilitates CRC metastasis in vivo and in vitro. Mechanistically, RNA-sequencing (RNA-seq) and RNA-binding protein immunoprecipitation-sequencing (RIP-seq) showed that DDX39B binds directly to the FUT3 pre-mRNA and upregulates FUT3 expression. Splicing experiments in vitro using a Minigene assay confirmed that DDX39B promotes FUT3 pre-mRNA splicing. A nuclear and cytoplasmic RNA separation assay indicates that DDX39B enhances the mRNA export of FUT3. Upregulation of FUT3 accelerates the fucosylation of TGFβR-I, which activates the TGFβ signaling pathway and eventually drives the epithelial–mesenchymal transition (EMT) program and contributes to CRC progression. These findings not only provide new insight into the role of DDX39B in mRNA splicing and export as well as in tumorigenesis, but also shed light on the effects of aberrant fucosylation on CRC progression.