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《基因组蛋白质组与生物信息学报(英文版)》 2013-06
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An Integrative Meta-analysis of MicroRNAs in Hepatocellular Carcinoma

Mahmoud ElHefnawi;Bangli Soliman;Nourhan Abu-Shahba;Marwa Amer;Centre of Excellence for Advanced Sciences,Informatics and Systems Department,National Research Centre;Stem Cells Research Group,Centre of Excellence for Advanced Sciences,Medical Molecular Genetics Department,National Research Centre;Biology Department,American University in Cairo (AUC);Faculty of Biotechnology,Misr University for Science and Technology (MUST);  
We aimed to shed new light on the roles of microRNAs(miRNAs) in liver cancer using an integrative in silico bioinformatics analysis. A new protocol for target prediction and functional analysis is presented and applied to the 26 highly differentially deregulated miRNAs in hepatocellular carcinoma. This framework comprises:(1) the overlap of prediction results by four out of fve target prediction tools, including TargetScan, PicTar, miRanda, DIANA-microT and miRDB(combining machine-learning, alignment, interaction energy and statistical tests in order to minimize false positives),(2) evidence from previous microarray analysis on the expression of these targets,(3) gene ontology(GO) and pathway enrichment analysis of the miRNA targets and their pathways and(4) linking these results to oncogenesis and cancer hallmarks. This yielded new insights into the roles of miRNAs in cancer hallmarks. Here we presented several key targets and hundreds of new targets that are signifcantly enriched in many new cancer-related hallmarks. In addition, we also revealed some known and new oncogenic pathways for liver cancer. These included the famous MAPK, TGFb and cell cycle pathways. New insights were also provided into Wnt signaling, prostate cancer, axon guidance and oocyte meiosis pathways. These signaling and developmental pathways crosstalk to regulate stem cell transformation and implicate a role of miRNAs in hepatic stem cell deregulation and cancer development. By analyzing their complete interactome, we proposed new categorization for some of these miRNAs as either tumor-suppressors or oncomiRs with dual roles. Therefore some of these miRNAs may be addressed as therapeutic targets or used as therapeutic agents. Such dual roles thus expand the view of miRNAs as active maintainers of cellular homeostasis.
【Fund】: partial support through Science and Technology Development Fund (STDF) by Egyptian Ministry of Scientifc Research (Grant No.1169 and 1679)
【CateGory Index】: R735.7
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【Citations】
Chinese Journal Full-text Database 1 Hits
1 CHEN Ya-jin1,MIN Jun1,SHANG Chang-zhen1,REN Meng2,PENG Xiao-xiong1,CAO Jun1,CHEN Ji-sheng11Department of Hepatobiliary Surgery,2Department of Endocrinology,the Second Affiliated Hospital,Sun Yat-sen University,Guangzhou 510120,China;MicroRNA Differential Expression Profile during Differentiation of Embryonic Stem Cells towards Hepatocytes Induced by Sodium Butyrate[J];Acta Academiae Medicinae Sinicae;2008-04
【Co-citations】
Chinese Journal Full-text Database 10 Hits
1 Li Rong,Chen Xuemei,He Junlin,Ding Yubin,Yang Dehui,Xu Hao,Zheng Anshun,Liu Xueqing(Department of Reproductive Biology,School of Public Health,Chongqing Medical University,Chongqing,400016,China);Hsa-miR-193b suppresses invasion of human endometrium adenocarcinoma HEC-1B cells[J];Journal of Third Military Medical University;2011-15
2 ZHOU Hong1,XU Wen2,CHEN Xiao-e1.1.Department of Dermatology,81 Hospital of PLA,Nanjing,Jiangsu 210002,China;2.Department of Dermatology,Nanjing Hospital of Jiangsu Province Corps,Chinese People’s Armed Police Forces,Nanjing,Jiangsu 210028,China;The clinical observation on the effects of four methods in the treatment of keloid[J];Military Medical Journal of Southeast China;2013-04
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4 Yongqi CUI;Qin GENG;Aiqin GU;Miaoxin ZHU;Hanwei KONG;Lei SUN;Lei LIU;Mingxia YAN;Ming YAO1;Yongqi CUI;Qin GENG;State Key Laboratory of Oncogenes and Related Genes,Shanghai Cancer Institute,Renji Hospital,Shanghai Jiaotong University School of Medicine;Thoracic Hospital Affiliated to Shanghai Jiaotong University;;Establishing the Nude Mice Bone Metastasis Model of Lung Adenocarcinoma and Applying MicroCT into the Observation[J];Chinese Journal of Lung Cancer;2013-09
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6 Patrick-Denis St-Coeur;Mohamed Touaibia;Miroslava Cuperlovic-Culf;Pier Jr Morin;Department of Chemistry and Biochemistry, Universite′ de Moncton,Moncton, NB E1A 3E9, Canada;National Research Council of Canada,Moncton, NB E1A 7R1, Canada;;Leveraging Metabolomics to Assess the Next Generation of Temozolomide-based Therapeutic Approaches for Glioblastomas[J];基因组蛋白质组与生物信息学报(英文版);2013-04
7 WANG Zhang - xun;ZHOU Quan;MENG Hui - ming;ZHANG Jun;HUANG Bo;School of Plant Protection,Anhui Agricultural University;Anhui Provincial Key Laboratory of Microbial Pest Control,Anhui Agricultural University;;Differential Expression Analysis of MicroRNA in Cicada Slough and Hemolymph Induction Conditions from Metarhizium anisopliae[J];Journal of Anhui Science and Technology University;2013-05
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【Secondary Citations】
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1 SHANG Chang-zhen,MIN Jun,ZHANG Lei,LIU Lu,DENG Xiao-geng,CHEN Ya-jin,CHEN Ji-sheng(Department of Hepatobiliary Surgery,The Second Affiliated Hospital of Sun Yat-sen University,Guangzhou 510120,China);Sodium butyrate induces mouse embryonic stem cells to differentiate into hepatocytes in vitro[J];Chinese Journal of Pathophysiology;2006-12
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