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健脾益气法对DEN大鼠肝癌后基因组转录调控的生物信息学分析 被引量:8

Study on the Mechanism of JianpiYiqi Decoction Regulating DEN- induced Hepatocarcinogenesis in Rats by Bioinformatic Analysis
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摘要 目的研究健脾益气法对DEN大鼠肝癌基因表达谱的影响,初步探讨健脾益气法治疗肝癌的分子机制。方法利用affymetrix NetAffxTM、DAVID和STRING等在线分析软件,对前期用Affymetrix Rat 230A GeneChip arrays检测到的不同中医治法干预后的DEN大鼠肝癌基因表达谱进行生物信息学分析。结果健脾益气法对肝癌基因表达的调节要明显优于其它治法,其调节的差异基因440个,包括上调表达130个和下调表达310个。这些差异基因编码蛋白在生物学过程中主要参与对有机物的应答反应和胞外刺激反应,在分子功能上主要参与特定蛋白的结合,而在信号通路中主要参与Gq蛋白激活的花生四烯酸-HETEs代谢通路;这些差异蛋白的相互作用主要集中在Adcy3、Gnao1、Tgfb1、Vim等15个基因的表达产物,结合文献挖掘发现健脾益气法对肝癌基因表达的调节主要表现在对TGF-β1诱导的上皮-间质转化(EMT)的下调、cAMP含量的上调和PPARα等核受体的逆向调节等,其中以TGF-β1-EMT蛋白网络相关分子在DEN大鼠肝癌中的表现及健脾益气法对其下调作用最明显。结论健脾益气法对DEN肝癌大鼠的治疗是多方位的;对TGF-β1诱导的肝癌EMT过程和Gq蛋白激活的花生四烯酸-HETEs代谢通路的下调作用可能是健脾益气法治疗肝癌的重要机制。 Objective To observe the regulation of Jianpi Yiqi decoction on the gene expression profile in DEN - induced rat hep- atoma, and to further explore the mechanism of Jianpi Yiqi decoction preventing primary liver cancer. Methods The microarray da- ta were obtained from normal rat liver,DEN -induced rat hepatoma before and after different TCM treatments by Affymetrix Rat 230A GeneChip arrays, and analyzed by bioinformatics methods using affymetrix NetAffxTM ,DAVID and STRING online tools. Re- sults Jianpi Yiqi decoction had a more significant effect on genes expression in DEN - induced rat hepatoma than other TCM treat- ments. All 440 differentially expressed genes, including 130 up -regulated and 310 down -regulated genes, which mainly related to identical protein binding, were - involved in various pathways included responding to extracellular stimulus and to organic sub- stance, and down - regulating Gq - activated arachidonic acid/HETEs metabolic pathway by DAVID analysis. The proteins interac- tions encoded by these genes were mainly focused on the 15 proteins ,including ADCY3 ,GNAOI .TGFB1 and VIM which were in- volved in TGF -βι -induced EMT, cAMP levels, and regulation of nuclear receptor by STRING analysis and literature mining. Conclusion The regulation of Jianpi Yiqi decoction preventing primary liver cancer involves multiple pathways, mainly including down - regulated TGF - βι - induced EMT and Gq - activated arachidonic acid/HETEs pathways.
出处 《时珍国医国药》 CAS CSCD 北大核心 2014年第7期1765-1768,共4页 Lishizhen Medicine and Materia Medica Research
基金 国家自然科学基金(No.30400582) 广西中医药大学重点课题(ZD10003)
关键词 肝癌 健脾益气治法 基因 生物信息学 Primary liver cancer JianpiYiqi Genes Bioinformatic analysis
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参考文献14

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