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        Exploring the Key Genes and Pathways of Osteoarthritis in Knee Cartilage in a Rat Model Using Gene Expression Profiling

        Yi-Ming Ren,Xin Zhao,Tao Yang,Yuan-Hui Duan,Yun-Bo Sun,Wen-Jun Zhao,Meng-Qiang Tian 연세대학교의과대학 2018 Yonsei medical journal Vol.59 No.6

        Purpose: To compare differentially expressed genes (DEGs) mediating osteoarthritis (OA) in knee cartilage and in normal kneecartilage in a rat model of OA and to identify their impact on molecular pathways associated with OA. Materials and Methods: A gene expression profile was downloaded from the Gene Expression Omnibus database. Analysis ofDEGs was carried out using GEO2R. Enrichment analyses were performed on the Gene Ontology (GO) and Kyoto Encyclopedia ofGenes and Genomes pathway using the Search Tool for the Retrieval of Interacting Genes database (http://www.string-db.org/). Subsequently, the regulatory interaction network of OA-associated genes was visualized using Cytoscape software (version 3.4.0;www.cytoscape.org). Results: In the gene expression profile GSE103416, a total of 99 DEGs were identified. Among them, 76 DEGs (76.77%) were overexpressed,and the remaining 23 DEGs (23.23%) were underexpressed. GO and pathway enrichment analyses of target geneswere performed. Using gene-gene interaction network analysis, relevant core genes, including MET, UBB, GNAI3, and GNA13,were shown to hold a potential relationship with the development of OA in cartilage. Using quantitative real-time PCR, the Gna13/cGMP-PKG signaling pathway was identified as a potential research target for therapy and for further understanding the developmentof OA. Conclusion: The results of the present study provide a comprehensive understanding of the roles of DEGs in knee cartilage in relationto the development of OA.

      • B3GNT2, a Polylactosamine Synthase, Regulates Glycosylation of EGFR in H7721 Human Hepatocellular Carcinoma Cells

        Qiu, Hao,Duan, Wei-Ming,Shu, Jie,Cheng, Hong-Xia,Wang, Wei-Ping,Huang, Xin-En,Chen, Hui-Li Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

        The epidermal growth factor receptor (EGFR) is an important surface receptor with N-glycans in its extracellular domain, whose glycosylation is essential for its function, especially in tumor cells. Here, we demonstrated that polylactosamine is markedly increased in H7721 hepatocellular carcinoma cells after treatment with EGF, while it apparently declined after exposure to all-trans retinoic acid (ATRA). In the study of the enzymatic mechanism of this phenomenon, we explored changes in the expression of poly-N-acetyllactosamine (PLN) branching glycosyltransferases using RT-PCR. Among the four glycosyltransferases with altered expression, GnT-V was most elevated by EGF, while GnT-V and B3GNT2 were most declined by ATRA. Next, we conducted co-immunoprecipitation experiments to test whether B3GNT2 and EGFR associate with each other. We observed that EGFR is a B3GNT2-targeting protein in H7721 cells. Taken together, these findings indicated that the altered expression of B3GNT2 will remodel the PLN stucture of EGFR in H7721 cells, which may modify downstream signal transduction.

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        Contributed Mini Review : New paradigms on siRNA local application

        ( Meng Pan ),( Jin Wen Ni ),( Hui Ming He ),( Shan Gao ),( Xiao Hong Duan ) 생화학분자생물학회(구 한국생화학분자생물학회) 2015 BMB Reports Vol.48 No.3

        Small interfering RNA (siRNA) functions through pairing with specific mRNA sequences and results in the mRNA`s degradation. It is a potential therapeutic approach for many diseases caused by altered gene expression. The delivery of siRNA is still a major problem due to its rapid degradation in the circulation. Various strategies have been proposed to help with the cellular uptake of siRNA and short or small hairpin RNA (shRNA). Here, we reviewed recently published data regarding local applications of siRNA. Compared with systemic delivery methods, local delivery of siRNA/shRNA has many advantages, such as targeting the specific tissues or organs, mimicking a gene knockout effect, or developing certain diseases models. The eye, brain, and tumor tissues are ‘hot’ target tissues/ organs for local siRNA delivery. The siRNA can be delivered locally, in naked form, with chemical modifications, or in formulations with viral or non-viral vectors, such as liposomes and nanoparticles. This review provides a comprehensive overview of RNAi local administration and potential future applications in clinical treatment. [BMB Reports 2015; 48(3): 147-152]

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        The SH2 domain is crucial for function of Fyn in neuronal migration and cortical lamination

        ( Xi Lu ),( Xin De Hu ),( Ling Zhen Song ),( Lei An ),( Ming Hui Duan ),( Shu Lin Chen ),( Shan Ting Zhao ) 생화학분자생물학회(구 한국생화학분자생물학회) 2015 BMB Reports Vol.48 No.2

        Neurons in the developing brain form the cortical plate (CP) in an inside-out manner, in which the late-born neurons are located more superficially than the early-born neurons. Fyn, a member of the Src family kinases, plays an important role in neuronal migration by binding to many substrates. However, the role of the Src-homology 2 (SH2) domain in function of Fyn in neuronal migration remains poorly understood. Here, we demonstrate that the SH2 domain is essential for the action of Fyn in neuronal migration and cortical lamination. A point mutation in the Fyn SH2 domain (FynR176A) impaired neuronal migration and their final location in the cerebral cortex, by inducing neuronal aggregation and branching. Thus, we provide the first evidence of the Fyn SH2 domain contributing to neuronal migration and neuronal morphogenesis. [BMB Reports 2015; 48(2): 97-102]

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