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Xin J.,Nankai University | Li J.,Nankai University | Feng Y.,Nankai University | Wang L.,University of Southampton | And 3 more authors.
OncoTargets and Therapy | Year: 2017

Myeloid differentiation is controlled by a multilayered regulatory circuitry consisting of various elements, including histone modifications, transcription factors, and posttranscriptional regulators such as miRNAs, long noncoding RNAs, and circular RNAs. However, the molecular mechanism underlying this biological process remains unclear. In this study, through epigenetic profiling analysis using chromatin immunoprecipitation (ChIP) followed by sequencing (ChIP-seq), we identified an lncRNA, HOTAIRM1, with a critical role in myeloid development. Further ChIP-chip analysis showed obvious H3K4me3 and H3K27me3 histone modification peak changes in the promoter region of HOTAIRM1 during the process of monocyte to dendritic cell (DC) differentiation. In line with this observation, HOTAIRM1 RNA expression was downregulated when monocytes differentiated into DCs. Moreover, we found that HOTAIRM1 RNA was regulated by epigenetic factors such as RBBP4 and RBBP7. Mechanistically, we found that the silencing of HOTAIRM1 caused changes in the expression of several monocyte differentiation markers such as CD14 and B7H2. In addition, based on the “competing endogenous RNA” hypothesis, we discovered miR-3960 targeting both HOTAIRM1 and the DC differentiation repression gene, HOXA1, by most possibly constructing a potential competing endogenous RNA network. Increased miR-3960 expression could downregulate both of these two long RNAs and finally lead peripheral blood cells to differentiate into DCs. In summary, our study demonstrates that HOTAIRM1 competitively binds to miR-3960 and finally regulates the process of hematopoiesis, which reveals a novel regulatory mechanism of lncRNA function. © 2017 Xin et al.

Li J.,Chinese Institute of Basic Medical Sciences | Zhu C.,Key Laboratory of Bioactive Materials | Yang J.,Key Laboratory of Bioactive Materials
Starch/Staerke | Year: 2015

Zwitterionic polymers are known to possess excellent protein resistance due to high hydration capacity of their zwitterionic moieties. In this study, polysaccharide-based zwitterionic polymers 3-dimethyl(propyl) ammonium propanesulfonate starches (Z-starches) with different degrees of substitution of the zwitterionic moieties (DSZM) were synthesized successfully. The value of DSZM can be controlled exactly in the range of 0-0.46. The cytotoxicity of Z-starches with different DSZM was evaluated by an MTT assay, and the Z-starch with DSZM of 0.26 promoted cell proliferation when the concentration of this polymer solution was 1-25mg/mL. The protein resistance and cell adhesion of Z-starch hydrogels were evaluated, and the amount of protein adsorption or cell adhesion on Z-starch hydrogels was decreased as the DSZM increased. The preliminary protein resistance and cell adhesion tests suggest that the Z-starches have potential applications in drug delivery carriers and coatings of implanted sensors where protein resistance is needed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Zhang M.,Key Laboratory of Bioactive Materials | Zhang M.,University of California at Irvine | Yang J.,Key Laboratory of Bioactive Materials | Jiang S.,University of California at Irvine | Cai B.,Key Laboratory of Bioactive Materials
Journal of Environmental Sciences | Year: 2010

An 8-month survey was conducted to detect and quantify enteroviruses in Tianjin coastal seawaters of Bohai Bay to assess coastal water quality. Ten water samples were collected from Bohai Bay for the detection and quantification of enteroviruses by conventional reverse transcription polymerase chain reaction (RT-PCR) and SYBR Green real-time quantitative RT-PCR (qRT-PCR). Total viral nucleic acid was extracted from 500 mL of seawater samples concentrated by Centricon plus-70 centrifugal filter devices. The viral recovery rate was 29.1% based on viral seeding study. The centrifugal ultrafiltration method applied is effective for viral recovery from small volume of polluted water, which may have broader applications to monitoring human virus in aquatic environment. Our results indicated that there was a severe viral contamination in seawater of Bohai Bay. Enteroviruses were detected at concentrations ranging from 1.7 × 106 to 6.3 × 107 copies/L by qRT-PCR. Sequencing analyses identified that all of the twenty clones as poliovirus type 2. This is the first quantitative report of human viruses in coastal waters of a metropolitan city in China. This study emphasized the importance for the local and central governments to monitor and assess the water quality. © 2010 The Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences.

Cui X.-A.,Tianjin Medical University | Liu X.,Tianjin Institute of Urological Surgery | Kong D.-L.,Key Laboratory of Bioactive Materials | Gu H.-Q.,Tianjin Medical University | Gu H.-Q.,Tianjin Institute of Urological Surgery
Chinese Journal of Biomedical Engineering | Year: 2012

This study aimed to prepare collagen/silk fibroin composite micro-nanofibers using electrospinning technique, and to evaluate their properties and cytocompatibility. Taking 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as solvent, the composite fibers were prepared according to the mass ratio of collagen/silk fibroin as 100:0, 70:30, 50:50, 30:70, 0:100, and then crosslinked by glutaraldehyde (GTA) vapor for 12 h. The fibers were characterized by combined techniques of scanning electron microscopy (SEM) , Fourier-transform infrared spectra (FTIR) , X-ray diffraction (XRD) , thermal analysis and tensile measurements. The composite fibers were inoculated with fibroblasts (3T3). The cell adhesion and proliferation were evaluated by SEM and MTT. The results showed the diameter of composite fibers ranged from 550 nm to 1100 nm, and fiber diameter was positively correlated with SF content. After crosslinking, the β-sheet structure, crystallinity and thermal stability of the nanofibers were improved. This improvement was more obvious with the SF content increases. The mechanical properties of cross-linked fibers were better than those of uncrosslinked fibers, and the best average ultimate tensile strength was (8.70 ± 1.05) MPa when SF content was 70%. The cells grew well on the surface of materials, and had the best adhesion and proliferation on the composite fibers with SF content of 70% , which might be a potential candidate for tissue engineering scaffold.

Cui X.A.,Tianjin Medical University | Liu X.,Tianjin Institute of Urological Surgery | Kong D.L.,Key Laboratory of Bioactive Materials | Gu H.Q.,Tianjin Institute of Urological Surgery
IFMBE Proceedings | Year: 2013

The electrospun collagen (COL)/silk fibroin (SF) complex scaffold was investigated for the fabrication of a biocompatible and biomimetic scaffold for tissue engineering. The COL/SF complex microfibers were prepared via electrospinning COL/SF blend solutions in 1,1,1,3,3,3-hexafluoroiso propanol (HFIP), and then crosslinked by glutaraldehyde (GTA) vapor. The fiber morphology was observed by scanning electron microscopy (SEM) and the structural changes of fibers after crosslinked were analysised by Fourier transform infrared spectra (FTIR). The mechanical property of the scaffolds was examined by tensile testing. To assay the biocompatibility of the matrics, the proliferation of fibroblasts (L929) on the microfibrous scaffolds was investigated by methylthiazol tetrazolium testing (MTT). The results showed that the average diameters of complex fibers ranged from 550 to 1100 nm, increasing with the increase of SF content. The GTA vapor stabilized the microfibers especially the COL component via crosslinking and stabilized the SF component via changing the SF component to β-sheet structure. The mechanical property of the crosslinked fibers was better than that of the uncrosslinked ones, and the highest average ultimate tensile strength 8.7 MPa appeared when SF content was 70%. L929 cells grew and proliferated well on the microfibers, especially on the fibers with SF content of 70%. These results strongly support that the COL/SF microfibrous scaffolds, could be a potential candidate for biomedical applications such as wound dressing and scaffolds for skin tissue engineering. © 2013 Springer-Verlag.

Mei S.,Nankai University | Liu Y.,Nankai University | Bao Y.,Nankai University | Zhang Y.,Nankai University | And 7 more authors.
PLoS ONE | Year: 2014

Introduction: Epigenetic modification plays a critical role in regulating gene expression. To understand how epigenetic modification alters miRNA expression in monocyte-derived dendritic cells (moDCs) in different environments, we analyzed the connections between H3K4me3 and H3K27me3 modification and the expression of miRNAs in LPS- and TGF-β-conditioned moDCs. Results: In moDCs, H3K4me3 modification was strongly associated with the expression of activating miRNAs, whereas H3K27me3 was related to repressive miRNAs. The regulation of miRNA expression by H3K4me3 and H3K27me3 was further confirmed by silencing or inhibiting methyltransferases or methylation- associated factors in LPS- and TGF-β-conditioned moDCs. siRNAs targeting H3K4me3-associated mixed lineage leukemia (MLL) and retinoblastoma binding protein 5 (RBBP5) reduced H3K4me3 enrichment and downregulated miRNA expression; conversely, silencing H3K27me3-associated enhancer of zeste homolog 2 (EZH2) and embryonic ectoderm development (EED) genes upregulated the DC-associated miRNAs. However, LPS-mediated miRNAs were often associated with H3K4me3 redistribution from the transcription start site (TSS) to the miRNA-coding region. Silencing LPS-associated NF-κB p65 and CBP/p300 not only inhibited H3K4m3 redistribution but also reduced miRNA expression. LPS-upregulated RBBP4 and RBBP7, which are involved in chromatin remodeling, also affected the redistribution of H3K4me3 and reduced the expression of miRNAs. Conclusion: In LPS- and TGF-β-conditioned moDCs, miRNAs may be modulated not only by H3K4m3 and H3K27me3 modification but also by redistribution of H3K4me3 around the transcriptional start site of miRNAs. Thus, H3K4me3 and H3K27me3 epigenetic modification may play an important role in regulating DC differentiation and function in the presence of tumor or inflammatory environments. © 2014 Mei et al.

Min S.,Nankai University | Li L.,Nankai University | Zhang M.,Nankai University | Zhang Y.,Nankai University | And 10 more authors.
Genes and Immunity | Year: 2012

The alterations induced in dendritic cells (DCs) in the cancer microenvironment have not been extensively explored. We found that the tumor-associated factor TGF-β may selectively upregulate the expression of miR-27a via the SP1 transcription factor. Importantly, miR-27a altered the activity of NF-κB and MAPKs (mitogen-activated protein kinases) p38, JNK (c-Jun N-terminal kinases) and ERK (extracellular signal-regulated kinase 1/2). It influences the production of proinflammatory cytokines by targeting TAB3, p38 MAPK, MAP2K4 and MAP2K7. As a consequence, miR-27a hampered the DC-mediated differentiation of Th1 and Th17 cells in vitro and in vivo, but it promoted the DC-mediated accumulation of Tr1 (CD4+ IL-10+) and Treg (CD4+ CD25+ Foxp3+) cells in vivo. The repeated infusion of miR-27a-engineered DCs into tumor tissues accelerated tumor growth, indicating that miR-27a is a potential target for tumor immunotherapy. © 2012 Macmillan Publishers Limited All rights reserved.

Cui W.,Key Laboratory of Bioactive Materials | Zhang Y.,Key Laboratory of Bioactive Materials | Hu N.,Key Laboratory of Bioactive Materials | Shan C.,Nankai University | And 4 more authors.
Cancer Biology and Therapy | Year: 2010

MicroRNAs (miRNAs) are non-coding RNAs that function as post-transcriptional gene regulators. MiRNAs play a pivotal role in cancer development. In the present study, we elucidated the roles of miR-520b and miR-520e in breast cancer cells involving complement attack. We examined the expression levels of miR-520b and miR-520e in immortalized breast cell line HBL-100 and in three breast cancer cell lines, including MCF-7, LM-MCF-7 and MDA-MB-231. The data showed that the expression levels of miR-520b and miR-520e in the three breast cancer cell lines were lower than that in HBL-100 cells, which were correlated with the less sensitivity of the breast cancer cell lines to complement-dependent cytotoxicity (CDC). While, we found that the overexpression of miR-520b and miR-520e could increase the sensitivity of the breast cancer cells to CDC, but the suppression of miR-520b and miR-520e mediated by anti-miRNAs could decrease the sensitivity of the breast cancer cells to CDC. Then, we identified that miR-520b and miR-520e were able to directly target the 3′untranslated regions (3'UTR) of the membrane-bound complement regulatory protein CD46, suggesting that miR-520b and miR-520e downregulate CD46 at post-transcriptional level. Enzyme-linked immunosorbent assay (ELISA) showed that the overexpression of miR-520b and miR-520e resulted in the increase of deposition of C3b mediated by downregulated CD46, suggesting that miRNA-520b and miR-520e involving CD46 mediate the cancer cell opsonization via an alternative pathway activation leading to CDC involving complement activation. Thus, we conclude that miR-520b and miR-520e contribute to CDC in breast cancer cells via directly targeting 3′UTR of CD46. © 2010 Landes Bioscience.

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