2011年博奥生物支持农业领域研究发表文献回顾 　　2011年，农牧林以及微生物领域相关文献共35篇（其中7篇文章IF>5），涉及国内外研究单位包括中国农业科学院、中国科学院、中国水稻研究所、中国农业大学、山东农业大学、华中农业大学、华南农业大学、河北农业大学、西北农林科技大学、广东省农业科学院、中山大学、中国中医科学院、徐州师范大学、西南大学、武汉大学、第二军医大学、南开大学、苏州大学、上海海洋大学、江苏科技大学、东南大学、纽卡斯大学等；涉及物种包括水稻、番茄、柑橘、丹参、棉花、拟南芥、猪、鸡、牛、兔子、家蚕、斑马鱼、梭子蟹、白色念珠菌、大肠杆菌、枯草芽孢杆菌等；在miRNA、mRNA、DNA等不同的分子水平进行不同方向的研究，如：抗逆抗病抗病毒机制研究、药物作用机理研究、目标基因调控机理研究、组织器官发育时空特异性研究、品种拷贝数差异研究等。   作者及文章题目 期刊 Chen,S.,et al.,Gene Expression Patterns in Different Wool Densities of Rex Rabbit Using cDNA Microarray. Agricultural Sciences in China, 2011, 10(4):595-601. Yang, C.,et al.,A regulatory gene induces trichome formation and embryo lethality in tomato. Proceedings of the National Academy of Sciences,2011,108: 11836 - 11841. Zhang, Z., et al., Arabidopsis floral initiator SKB1 confers high salt tolerance by regulating transcription and pre-mRNA splicing through altering histone H4R3 and small nuclear ribonucleoprotein LSM4 methylation. Plant Cell, 2011,23:396-411. Wang,J.,et al., Integrated Transcriptional and Proteomic Analysis with In Vitro Biochemical Assay Reveal the Important Role of CYP3A46 in T-2 Toxin Hydroxylation in Porcine Primary Hepatocytes. Molecular & Cellular Proteomics,2011,10: M111.008748. Cui,Y.,et al.,The molecular mechanism of action of bactericidal gold nanoparticles on Escherichia coli. Biomaterials,2011,online Wang,Y.,et al., Cytokinin antagonizes ABA suppression to seed germination of Arabidopsis by downregulating ABI5 expression. The Plant Journal,2011,68(2): 249–261. Zou,L.,et al., Leaf Rolling Controlled by the Homeodomain Leucine Zipper Class IV Gene Roc5 in Rice. Plant Physiology, 2011,156: 1589 - 1602. Yao,T.,et al.,MiR-21 is involved in cervical squamous cell tumorigenesis and regulates CCL20. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2012,1822(2):248-260. Li,Z.,et al.,High invertase activity in tomato reproductive organs correlates with enhanced sucrose import into, and heat tolerance of, young fruit. Journal of Experimental Botany,2011,online. Yu, P., et al., Detection of copy number variations in rice using array-based comparative genomic hybridization. BMC Genomics, 2011,12（1）: 372. Zhu,L.,et al., Identification and characterization of SHORTENED UPPERMOST INTERNODE 1, a gene negatively regulating uppermost internode elongation in rice. Plant Molecular Biology, 2011,77(4-5):475-87. Hu, F., et al., Identification of rhizome-specific genes by genome-wide differential expression Analysis in Oryza longistaminata. BMC Plant Biology, 2011,11:18. Li,T.,et al.,A systematic analysis of the skeletal muscle miRNA transcriptome of chicken varieties with divergent skeletal muscle growth identifies novel miRNAs and differentially expressed miRNAs. BMC Genomics, 2011,12(1):186. Wang,D.,et al.,Genome-wide temporal-spatial gene expression profiling of drought responsiveness in rice. BMC Genomics, 2011, 12(1):149. Sun,X.,et al.,Microarray profiling for differential gene expression in PMSG-hCG stimulated preovulatory ovarian follicles of Chinese Taihu and Large White sows BMC Genomics, 2011,12(1):111. Chen,C.,et al.,Transcriptional profiling of host gene expression in chicken liver tissues infected with oncogenic Marek’s disease virus. Journal of General Virology ,2011,92(12):2724-2733. Lü,A.,et al.,Gene expression profiling in the skin of zebrafish infected with Citrobacter freundii. Fish & Shellfish Immunology,2011,online Liang, R., et al., 2-Amino-nonyl-6-methoxyl-tetralin muriate activity against Candida albicans augments endogenous reactive oxygen species production – a microarray analysis study. FEBS Journal, 2011,278(7):1075-1085. Gan,L.,et al.,Microarray-based gene expression profiles of silkworm brains. BMC Neuroscience, 2011, 12(1):8. Jin,W.,et al.,Microarray-based Analysis of Tomato miRNA Regulated by Botrytis cinerea. Journal of Plant Growth Regulation, 2011,1-9. Zhou,T.,et al.,Global transcriptional responses of Bacillus subtilis to xenocoumacin 1. Journal of Applied Microbiology,2011,111(3):652-62. Zhang,J.,et al., Identification of miRNAs and Their Target Genes Using Deep Sequencing and Degradome Analysis in Trifoliate Orange [Poncirus trifoliate (L.) Raf]. Molecular Biotechnology, 2011,online. Cui,G.,et al.,Candidate genes involved in tanshinone biosynthesis in hairy roots of Salvia miltiorrhiza revealed by cDNA microarray. Molecular Biology Reports, 2011,38(4):2471-2478. Li,A.,et al.,Gene expression profiles of two intraspecific Larix lines and their reciprocal hybrids. Molecular Biology Reports,2011,online Wu, P., et al., Microarray analysis of the gene expression profile in the midgut of silkworm infected with cytoplasmic polyhedrosis virus. Molecular Biology Reports, 2011,38(1):333-341. Xu,Q.,et al.,Gene expression profiles of the swimming crab Portunus trituberculatus exposed to salinity stress. Marine Biology,2011,158(1):2161-2172. Yin,Z.,et al.,Difference in miRNA expression profiles between two cotton cultivars with distinct salt sensitivity. Molecular Biology Reports, 2011,Online Li,X.,et al., Characterization and expression analysis of the SNF2 family genes in response to phytohormones and abiotic stresses in rice. Biologia Plantarum,2011,55(4):625-633. Wang, Y.,et al.,Gene Expression Analysis from Phoxim-induced Domesticated Silkworm (Bombyx mori) by Whole-Genome Oligonucleotide Microarray. Pesticide Biochemistry and Physiology, 2011,online. Zhang,Y.,et al.,Differentially expressed genes in skeletal muscle tissues from castrated Qinchuan cattle males compared with those from intact males. Livestock Science,2011,135(1):76-83. Jiang, H., et al., Overexpression of SGR results in oxidative stress and lesion-mimic cell death in rice seedlings. Journal of Integrative Plant Biology，2011，53(5):375-87. Cai,H.,et al., Transcriptome response to phosphorus starvation in rice. Acta Physiologiae Plantarum, 2011,online. Dong,H.,et al.,Regulating effects and mechanisms of Chinese medicine decoction on growth and gut hormone expression in heat stressed pigs. Livestock Science, 2011,online. Zhao, M., et al., Global expression profile of silkworm genes from larval to pupal stages: Toward a comprehensive understanding of sexual differences. Insect Science，2011,18(6):607-618. Zeng,J.,et al.,Transcriptome analysis of fruit development of a citrus late-ripening mutant by microarray. Scientia Horticulturae,2011,online  

　　乙型肝炎病毒（hepatitis B virus，HBV）感染可引起肝脏的急性和慢性炎症。急性感染一般表现为自限性肝炎，除爆发性肝炎外，对人体的危害较小；而慢性感染则与肝硬化（cirrhosis）和原发性肝癌（hepatocellular carcinoma，HCC）的发生密切相关。全球约有3.5亿的HBV携带者，最终发展为肝癌的比例高达25%，每年死于HBV相关肝癌的患者高达100多万。中国为HBV高度流行的国家，HBV感染是严重危害国民健康和生活质量的重要传染性疾病。 　　MicroRNA 是一类小的非编码RNA，可通过降解靶mRNA和抑制靶mRNA翻译等方式调控基因表达，在动植物的生长发育、肿瘤的发生发展、感染性疾病的发生发展中有重要作用。近年来的研究发现，microRNA 参与了HCV病毒、HIV病毒、EB病毒、Plum pox病毒、CMV病毒、Kaposi's 肉瘤相关病毒等病毒在宿主细胞内的复制过程，调控宿主细胞与病毒的相互作用，影响疾病的发生发展及转归，有可能成为新的抗病毒治疗靶点。程京教授课题组、郭永副研究员与北京大学人民医院魏来教授、重庆医科大学黄爱龙教授课题组合作，利用生物芯片平台结合功能研究发现miR-372/373这簇小RNA可通过调控宿主细胞的转录因子促进HBV表达。该研究通过将microRNA和转录因子这两类细胞内非常重要的调控因子相关联，为HBV表达调控研究提供了新的方向，具有重要的理论意义。   　　上述研究的博奥生物晶芯®哺乳动物miRNA芯片服务与Real time RT-PCR服务在博奥生物有限公司完成。 原文摘要：   　　MicroRNAs-372/373 promote the expression of hepatitis B virus through the targeting of nuclear factor I/B   MicroRNAs (miRNAs) play important roles in the posttranscriptional regulation of gene expression. Recent evidence has indicated the pathological relevance of miRNA dysregulation in hepatitis virus infection; however, the roles of microRNAs in the regulation of hepatitis B virus (HBV) expression are still largely unknown. In this study we identified that miR-373 was up-regulated in HBV-infected liver tissues and that the members of the miRs-371-372-373 (miRs-371-3) gene cluster were also significantly co-up-regulated in HBV-producing HepG2.2.15 cells. A positive in vivo association was identified between hepatic HBV DNA levels and the copy number variation of the miRs-371-3 gene cluster. The enhanced expression of miRs-372/373 stimulated the production of HBV proteins and HBV core-associated DNA in HepG2 cells transfected with 1.33HBV. Further, nuclear factor I/B (NFIB) was identified to be a direct functional target of miRs-372/373 by in silico algorithms and this was subsequently confirmed by western blotting and luciferase reporter assays. Knockdown of NFIB by small interfering RNA (siRNA) promoted HBV expression, whereas rescue of NFIB attenuated the stimulation in the 1.3xHBV-transfected HepG2 cells. Conclusion: Our study revealed that miRNA (miRs-372/373) can promote HBV expression through a pathway involving the transcription factor (NFIB). This novel model provides new insights into the molecular basis in HBV and host interaction.   原文出处：http://onlinelibrary.wiley.com/doi/10.1002/hep.24441/abstract;jsessionid=6B0DBCF4745EF5CB4D33C995287182BA.d01t04  

　　世界上每年有超过160万例肺癌新发病例，超过137万人死于肺癌。中国每年有52万例肺癌新发病例，超过45万人死于肺癌。80%肺癌是非小细胞肺癌，非小细胞肺癌中40%是鳞癌。ⅠA期肺鳞癌患者的5年存活率约为60%，而Ⅱ-Ⅳ期肺鳞癌患者的5年存活率为5% - 40%。因此，发现新的标志物并应用于早期诊断和预后对于提高肺鳞癌患者的生存率具有重要意义。 　　中国医学科学院肿瘤研究所赫捷教授与清华大学郭永副研究员合作利用microRNA芯片系统的比较了60对肺鳞癌和癌旁组织microRNA表达谱的差异，发现了一个包含5个microRNA的分类器（hsa-miR-210, hsa-miR-182, hsa-miR-486-5p, hsa-miR-30a and hsa-miR-140-3p)。该分类器区分肺鳞癌和正常肺组织的准确率超过94%。与此同时，他们还发现hsa-miR-31的表达量与病人的存活期负相关。DICER1基因是hsa-miR-31的靶基因。 　　上述研究的博奥生物晶芯®哺乳动物miRNA芯片服务与Real time RT-PCR服务在博奥生物有限公司完成。 原文摘要： 　　A 5-MicroRNA Signature for Lung Squamous Cell Carcinoma Diagnosis and hsa-miR-31 for Prognosis   　　Purpose: Recent studies have suggested that microRNA biomarkers could be useful for stratifying lung cancer subtypes, but microRNA signatures varied between different populations. Squamous cell carcinoma (SCC) is one major subtype of lung cancer that urgently needs biomarkers to aid patient management. Here, we undertook the first comprehensive investigation on microRNA in Chinese SCC patients. Experimental Design: MicroRNA expression was measured in cancerous and noncancerous tissue pairs strictly collected from Chinese SCC patients (stages I–III), who had not been treated with chemotherapy or radiotherapy prior to surgery. The molecular targets of proposed microRNA were further examined. 　　Results: We identified a 5-microRNA classifier (hsa-miR-210, hsa-miR-182, hsa-miR-486-5p, hsa-miR-30a, and hsa-miR-140-3p) that could distinguish SCC from normal lung tissues. The classifier had an accuracy of 94.1% in a training cohort (34 patients) and 96.2% in a test cohort (26 patients). We also showed that high expression of hsa-miR-31 was associated with poor survival in these 60 SCC patients by Kaplan–Meier analysis (P = 0.007), by univariate Cox analysis (P = 0.011), and by multivariate Cox analysis (P = 0.011). This association was independently validated in a separate cohort of 88 SCC patients (P = 0.008, 0.011, and 0.003 in Kaplan–Meier analysis, univariate Cox analysis, and multivariate Cox analysis, respectively). We then determined that the tumor suppressor DICER1 is a target of hsa-miR-31. Expression of hsa-miR-31 in a human lung cancer cell line repressed DICER1 activity but not PPP2R2A or LATS2. 　　Conclusions: Our results identified a new diagnostic microRNA classifier for SCC among Chinese patients and a new prognostic biomarker, hsa-miR-31. 原文出处：http://clincancerres.aacrjournals.org/content/17/21/6802.abstract  

　　宫颈癌（cervical carcinoma）是女性第二大恶性肿瘤，并且在年轻女性中发病率高。2002年全世界的新发病例为50万人，死亡病例为27万人。根据中国疾病预防与控制中心公布的数据，我国每年宫颈癌新发病例为13.15 万人，约占世界总数的26%，死亡病例为5.3 万人，约占世界总数的20%。因此，我国的宫颈癌防治形势非常严峻。   　　在99.8%的宫颈癌患者中均可检测到HPV感染。但单独的HPV 感染不足以引起宫颈癌，细胞本身必须发生相应的变化，才能最终引起宫颈癌。清华大学的程京教授与新疆医科大学第一附属医院的温浩教授合作，利用生物芯片平台研究了宫颈癌组织中microRNA的表达变化，发现了20种microRNA在宫颈癌的发生和发展过程中表达量发生了改变。其中microRNA-133b在从宫颈上皮内瘤样病变到侵润癌的发展过程中，表达量逐步升高。功能学实验结果表明，这一microRNA具有促进宫颈癌发生和发展的作用。该microRNA有可能作为临床早期诊断的新型宫颈癌标志物。 　　上述研究成果已申请专利，研究论文已在Oncogene杂志网站在线发表。其中的博奥生物晶芯®哺乳动物miRNA芯片服务与Real time RT-PCR服务在博奥生物有限公司完成。 原文摘要： 　　MicroRNA-133b is a key promoter of cervical carcinoma development through the activation of the ERK and AKT1 pathways   　　We report that elevated microRNA-133b (miR-133b) acts as an oncogene in human cervical carcinoma to promote tumorigenesis and metastasis. In situ hybridization confirmed that miR-133b is localized in proliferating human cervical carcinoma cells with levels progressively elevating throughout advancing stages. Cellular studies showed that miR-133b enhances cell proliferation and colony formation by targeting mammalian sterile 20-like kinase 2 (MST2), cell division control protein 42 homolog (CDC42) and ras homolog gene family member A (RHOA), which subsequently results in activation of the tumorigenic protein kinase B alpha (AKT1) and mitogenactivated protein kinase (ERK1 and ERK2, here abbreviated as ERK) signaling pathways. Mouse experiments revealed that upregulation of miR-133b in cervical carcinoma cells strongly promotes both in vivo tumorigenesis and independent metastasis to the mouse lung. The data indicates that upregulation of miR-133b shortens the latency of cervical carcinoma. Together, these findings suggest that miR-133b could be a potent marker for the early onset of cervical carcinoma.   原文出处：http://www.nature.com/onc/journal/vaop/ncurrent/abs/onc2011561a.html