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The Gut Microbiota, Tumorigenesis, and Liver Diseases

Engineering 2017年第1期3卷 110-114页

作者： Guishuai Lv Ningtao Cheng Hongyang Wang International Cooperation laboratory on signal transduction Eastern Hepatobiliary Surgery Institute Second Military Medical University Shanghai 200438 China National Center for Liver Cancer Shanghai 201805 China

In recent decades, diseases concerning the gut microbiota have presented some of the most serious public health problems worldwide. The human host＇s physiological status is influenced by the intestinal microbiome, thus integrating external factors, such as diet, with genetic and immune signals. The notion that chronic inflammation drives carcinogenesis has been widely established for various tissues. It is surprising that the role of the microbiota in tumorigenesis has only recently been recognized, given that the presence of bacteria at tumor sites was first described more than a century ago. Extensive epidemiological studies have revealed that there is a strong link between the gut microbiota and some common cancers. However, the exact molecular mechanisms linking the gut microbiota and cancer are not yet fully understood. Changes to the gut microbiota are instrumental in determining the occurrence and progression of hepatocarcinoma, chronic liver diseases related to alcohol, nonalcoholic fatty liver disease （NAFLD）, and cirrhosis. To be specific, the gut milieu may play an important role in systemic inflammation, endotoxemia, and vasodilation, which leads to complications such as spontaneous bacterial peritonitis and hepatic encephalopathy. Relevant animal studies involving gut microbiota manipulations, combined with observational studies on patients with NAFLD, have provided ample evidence pointing to the contribution of dysbiosis to the pathogenesis of NAFLD. Given the poor prognosis of these clinical events, their prevention and early management are essential. Studies of the composition and function of the gut microbiota could shed some light on understanding the prognosis because the microbiota serves as an essential component of the gut milieu that can impact the aforementioned clinical events. As far as disease management is concerned, probiotics may provide a novel direction for therapeutics for hepatocellular carcinoma （HCC） and NAFLD, given that probioti

关键词： Gut microbiota Dysbiosis Tumorigenesis Hepatocellular carcinoma Nonalcoholic fatty liver disease

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HCCDB: A Database of Hepatocellular Carcinoma Expression Atlas

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Genomics, Proteomics & Bioinformatics 2018年第4期16卷 269-275页

作者： Qiuyu Lian Shicheng Wang Guchao Zhang Dongfang Wang Guijuan Luo Jing Tang Lei Chen Jin Gu MOE Key laboratory of Bioinformatics Beijing National Research Center for Information Science and TechnologyBioinformatics Division Department of Automation Tsinghua University International Co-operation laboratory on signal transduction Eastern Hepatobiliary Surgery Institute Second Military Medical University

Hepatocellular carcinoma （HCC） is highly heterogeneous in nature and has been one of the most common cancer types worldwide. To ensure repeatability of identified gene expression patterns and comprehensively annotate the transcriptomes of HCC, we carefully curated 15 public HCC expression datasets that cover around 4000 clinical samples and developed the database HCCDB to serve as a one-stop online resource for exploring HCC gene expression with userfriendly interfaces. The global differential gene expression landscape of HCC was established by analyzing the consistently differentially expressed genes across multiple datasets. Moreover, a 4D metric was proposed to fully characterize the expression pattern of each gene by integrating data from The Cancer Genome Atlas （TCGA） and Genotype-Tissue Expression （GTEx）. To facilitate a comprehensive understanding of gene expression patterns in HCC, HCCDB also provides links to third-party databases on drug, proteomics, and literatures, and graphically displays the results from computational analyses, including differential expression analysis, tissue-specific and tumorspecific expression analysis, survival analysis, and co-expression analysis. HCCDB is freely accessible at http：//***/database/hccdb.

关键词： Hepatocellular carcinoma Database Transcriptome Integrative analysis Meta-analysis

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The in vitro reconstitution of nucleosome and its binding patterns with HMG1/2 and HMG14/17 proteins

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Cell Research 2003年第5期13卷 351-359页

作者： SHU BING ZHANG, JIAN HUANG, HUI ZHAO, YI ZHANG, CHUN HuI HOU, XIAO DONG CHENG, CHU JIANG, MIN QIAN LI, JUN HU, RUO LAN QIAN 1 Group of Globin gene Expression and regulation, State Key laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. 2 Shanghai Institute of Nuclear Research, Chinese Academy of Sciences, Shanghai 201800, China Group of Globin gene Expression and regulation State Key Laboratory of Molecular Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China

Using atomic force microscopy (AFM), the dynamic process of the in vitro nucleosome reconstitution followed by slow dilution from high salt to low salt was visualized. Data showed that the histone octamers were dissociated from DNA at 1M NaCl. When the salt concentration was slowly reduced to 650 mM and 300 mM, the core histones bound to the naked DNA gradually. Once the salt concentration was reduced to 50 mM the classic 'beads-on-astring' structure was clearly visualized. Furthermore, using the technique of the in vitro reconstitution of nucleosome, the mono- and di- nucleosomes were assembled in vitro with both HS2core (-10681 to -10970 bp) and NCR2 (-372 to -194 bp) DNA sequences in the 5’flanking sequence of human b-globin gene. Data revealed that HMG 1/2 and HMG 14/17 proteins binding to both DNA sequences are changeable following the assembly and disassembly of nucleosomes. We suggest that the changeable binding patterns of HMG 14/17 and HMG1/2 proteins with these regulatory elements may be criti

关键词： atomic force microscopy HMG proteins (HMG1/2 and HMG14/17) human β-globin gene in vitro reconstitution nucleosome.

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Cloning and Expression of Intracellular Part of Receptor Protein Tyrosine Phosphatase RPTPα and Preparation of Its Polyclonal Antibodies

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Chemical Research in Chinese Universities 2008年第3期24卷 344-347页

作者： CHEN Yang YANG Su-juan FU Yao WANG Jia-peng ZHAO Zhi-zhuang FU Xue-qi Edmond H. Fischer signal transduction laboratory College of Life Sciences Jiltin University Changchun 130012 P R. China University of Oklahoma Health Science Centel Oklahoma 73104 USA

A DNA fragment encoding the intracellular part of tyrosine phosphatase RPTPα designated as RPTPα-2D gene was amplified by PCR from a human prostate cDNA library and cloned into the pT7 E. coli expression vector. The resulting plasmid pT7-RPTPα-2D was used to transform Rosetta DE3 E. coli cells. RPTPα-2D was predominately expressed in the insoluble inclusion body and was effectively purified using preparative electrophoresis gels. Polyclonal antibodies were obtained after immunization of a rabbit with purified RPTPα-2D. The antibodies displayed a high titer and sensitivity. This study thus provided a valuable tool for further researches on RPTPα.

关键词： Receptor-like protein tyrosine phosphatase Clone Polyclonal antibodies

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Small auxin-up RNA gene OsSAUR33 promotes seed aging tolerance in rice

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Journal of Integrative Agriculture 2025年第1期24卷 61-71页

作者： Shan Sun Wenjun Li Yanfen Fang Qianqian Huang Zhibo Huang Chengjing Wang Jia Zhao Yongqi He Zhoufei Wang laboratory of Seed Science and Technology South China Agricultural University/Guangdong Key Laboratory of Plant Molecular Breeding/State Key Laboratory for Conservation and Utilization of Subtropical Agro-BioresourcesGuangzhou 510642China School of Agriculture Yunnan UniversityKunming 650091China

Seed aging tolerance during storage is generally an important trait for crop production, yet the role of small auxin-up RNA genes in conferring seed aging tolerance is largely unknown in rice. In this study, one small auxin-up RNA gene, OsSAUR33, was found to be involved in the regulation of seed aging tolerance in rice. The expression of OsSAUR33 was significantly induced in aged seeds compared with unaged seeds during the seed germination phase. Accordingly, the disruption of OsSAUR33 significantly reduced seed vigor compared to the wild type(WT) in response to natural storage or artificial aging treatments. The rice OsSAUR33 gene promotes the vigor of aged seeds by enhancing their reactive oxygen species(ROS) level during seed germination, and the accumulation of ROS was significantly delayed in the aged seeds of Ossaur33 mutants in comparison with WT during seed germination. Hydrogen peroxide(H_(2)O_(2)) treatments promoted the vigor of aged seeds in various rice varieties. Our results provide timely theoretical and technical insights for the trait improvement of seed aging tolerance in rice.

关键词： auxin-responsive gene reactive oxygen species rice seed aging seed vigor

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Ribosome profiling analysis identified a KRAS-interacting microprotein that represses oncogenic signaling in hepatocellular carcinoma cells

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Science China(Life Sciences) 2020年第4期63卷 529-542页

作者： Wenli Xu Bing Deng Penghui Lin Chang Liu Bin Li Qiaojuan Huang Hui Zhou Jianhua Yang Lianghu Qu MOE Key laboratory of gene Function and regulation State Key Laboratory for BiocontrolSchool of Life SciencesSun Yat-Sen UniversityGuangzhou 510275China The Fifth Affiliated Hospital Sun Yat-Sen UniversityZhuhai 519000China

The roles of concealed microproteins encoded by long noncoding RNAs(lncRNAs)are gradually being exposed,but their functions in tumorigenesis are still largely ***,we identify and characterize a conserved 99-amino acid microprotein named KRASIM that is encoded by the putative lncRNA *** is differentially expressed in normal hepatocytes and hepatocellular carcinoma(HCC)cells and can suppress HCC cell growth and ***,KRASIM interacts and colocalizes with the KRAS protein in the cytoplasm of human HuH-7 hepatoma *** importantly,the overexpression of KRASIM decreases the KRAS protein level,leading to the inhibition of ERK signaling activity in HCC *** results demonstrate a novel microprotein repressor of the KRAS pathway for the first time and provide new insights into the regulatory mechanisms of oncogenic signaling and HCC therapy.

关键词： KRAS lncRNA microprotein ribosome profiling hepatocellular carcinoma

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Diverse functions of sox9 in liver development and homeostasis and hepatobiliary diseases

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genes & Diseases 2024年第4期11卷 170-187页

作者： Taiyu Shang Tianyi Jiang Xiaowen Cui Yufei Pan Xiaofan Feng Liwei Dong Hongyang Wang School of Life Sciences Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China National Center for Liver Cancer The Naval Medical UniversityShanghai 201805China International Cooperation laboratory on signal transduction Eastern Hepatobiliary Surgery InstituteThe Second Military Medical UniversityShanghai 200438China laboratory of signaling regulation and Targeting Therapy of Liver Cancer Second Military Medical University&Ministryof EducationShanghai 200438China

The liver is the central organ for digestion and detoxification and has unique metabolic and regenerative *** hepatobiliary system originates from the foregut endoderm,in which cells undergo multiple events of cell proliferation,migration,and differentiation to form the liver parenchyma and ductal system under the hierarchical regulation of transcription *** on liver development and diseases have revealed that SRY-related high-mobility group box 9(SOx9)plays an important role in liver embryogenesis and the progression of hepatobiliary ***9 is not only a master regulator of cell fate determination and tissue morphogenesis,but also regulates various biological features of cancer,including cancer stemness,invasion,and drug resistance,making Sox9 a potential biomarker for tumor prognosis and *** review systematically summarizes the latest findings of sox9 in hepatobiliary development,homeostasis,and *** also highlight the value of sox9 as a novel biomarker and potential target for the clinical treatment of major liverdiseases.

关键词： Biliary system Cancer Homeostasis Liver diseases SOX9

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Editorial for the Special Issue on New Technology of Tumor Diagnosis and Treatment

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Engineering 2021年第10期7卷 1343-1344页

作者： Hongyang Wang Shengli Yang Fudan University Shanghai Cancer Center Shanghai 200032China International Cooperation laboratory on signal transduction&Key laboratory of signaling regulation and Targeting Therapy of Liver Cancer Ministry of Education&Shanghai Key Laboratory of Hepatobiliary Tumor BiologyEastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai 200438China Shanghai Institute Nutrition and Health Chinese Academy of SciencesShanghai 200031China

Cancer is a global public health threat and a leading cause of death in *** 2020,the number of new cancer cases around the world reached approximately 19.3 million,and about 10.0 million cancer-related deaths *** diagnosis and treatment remain a huge challenge due to the diversity of cancer etiology,the complicated mechanism and long process of tumorigenesis,and the significant heterogeneity between *** cancer is a systemic disease,tumor diagnosis is *** treatment has evolved from the initial conventional surgery,radiotherapy,and chemotherapy to the current multimethod and multidisciplinary comprehensive *** the continuous deepening and advancement of research in disease biology,we have gained a better understanding of cancer.

关键词： diagnosis chemotherapy treatment

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A twist in the tale:global insights into archaeal box C/D RNA-guided 2′-O-methylation

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Science China(Life Sciences) 2024年第4期67卷 849-850页

作者： Bin Li Jianhua Yang MOE Key laboratory of gene Function and regulation State Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-sen UniversityGuangzhou 510275China The Fifth Affiliated Hospital Sun Yat-sen UniversityZhuhai 519000China

The 2′-O-methylation of RNA stands as a dynamic and multifaceted modification,wielding significant influence over the regulation of RNA function,stability,and interactions within the cellular context(Sun et al.,2023)... 详细信息

关键词： twist insight

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Split Nano luciferase complementation for probing protein-protein interactions in plant cells

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Journal of Integrative Plant Biology 2020年第8期62卷 1065-1079页

作者： Feng-Zhu Wang Nannan Zhang Yan-Jun Guo Ben-Qiang Gong Jian-Feng Li Guangdong Provincial Key laboratory of Plant Resources State Key Laboratory of BiocontrolMOE Key Laboratory of Gene Function and RegulationSchool of Life SciencesSun Yat‐sen UniversityGuangzhou 510275China Guangdong Provincial Key laboratory of Sugarcane Improvement and Biorefinery Guangdong Bioengineering InstituteGuangzhou 510316China

Deciphering protein-protein interactions(PPIs)is fundamental for understanding signal transduction pathways in *** split firefly luciferase(Fluc)complementation(SLC)assay has been widely used for analyzing ***,concern has risen about the bulky halves of Fluc interfering with the functions of their fusion *** luciferase(Nluc)is the smallest substitute for Fluc with improved stability and ***,we developed a dual-use system enabling the detection of PPIs through the Nluc-based SLC and co-immunoprecipitation *** was realized by coexpression of two proteins under investigation in fusion with the HA-or FLAG-tagged Nluc halves,*** validated the robustness of this system by reproducing multiple previously documented PPIs in protoplasts or Agrobacterium-transformed *** next applied this system to evaluate the homodimerization of Arabidopsis CERK1,a coreceptor of fungal elicitor chitin,and its heterodimerization with other homologs in the absence or presence of ***,split fragments of Nluc were fused to two cytosolic ends of Arabidopsis calcium channels CNGC2 and CNGC4 to help sense the allosteric change induced by the bacterial elicitor ***,these results demonstrate the usefulness of the Nluc-based SLC assay for probing constitutive or inducible PPIs and protein allostery in plant cells.

关键词： system interactions Arabidopsis

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