microRNA在急性胰腺炎患者外周血中表达的意义

目的 通过检测血清microRNA变化,预判急性胰腺炎的病情严重度并探讨影响经皮置管引流(PCD)治疗的因素.方法 回顾性分析2013年10月至2014年3月成都军区总医院收治的120例急性胰腺炎患者的临床资料并采集其外周血,35例急性重度胰腺炎(SAP)、急性中重度胰腺炎(MSAP)为A组,85例急性轻度胰腺炎(MAP)为B组.对所有患者进行APACHE Ⅱ、Reason、BISAP评分,用实时定量PCR法进行定量检测患者血清中miR-146a、miR-10b、miR-21、miR-26a表达水平,比较两组之间的4种microRNA表达差异以及与评分系统间的相关性,并分析影响PCD治疗的因素.计量资料采用t检验,变量间关系采用直线相关分析.单因素和多因素分析采用Logistic回归.结果 (1)APACHEⅡ、RANSON、BISAP评分:A组分别为(8.28±0.61)分、(3.42±0.54)分、(1.71±0.32)分;B组分别为(3.18±0.52)分、(1.43±0.25)分、(0.37±0.06)分,两组比较,差异有统计学意义(t=4.266,7.809,4.113,P＜0.05).(2)血清miR-146a、miR-10b、miR-21、miR-26a表达水平:A组分别为1.41±0.21、2.94±0.49、1.62±0.25、1.21±0.20;B组分别为6.29±0.91、0.52±0.09、2.82±0.33、3.57±0.64.miR-146a、miR-10b在两组间差异有统计学意义(=-2.156,2.110,P＜0.05),而miR-21、miR-26a两组间差异无统计学意义(t=-1.114,-1.571,P ＞0.05).(3)相关性:A组miR-146a、miR-10b与APACHEⅡ、RANSON、BISAP评分有相关性(r=-0.826、0.837,-0.874、0.866,-0.833、0.899,P＜0.05).而miR-21、miR-26a表达水平与APACHE Ⅱ、RANSON、BISAP评分无相关性(r=0.642、0.321,0.701、0.750,0.716、0.716,P＞0.05).B组miR-146a、miR-10b、miR-21、miR-26a表达水平与APACHE Ⅱ评分无相关性(r=0.067,0.347,0.133,0.111,P＞0.05);与RANSON评分无相关性(r =0.178,0.078,0.092,0.142,P＞0.05);与BISAP评分无相关性(r=0.103,0.260,0.216,0.285,P＞0.05).(4)预测因素分析:单因素Logistic回归分析发现RANSON评分、BISAP评分、miR-10b是影响PCD干预的因素(OR =4.170,5.612,2.500;95％可信区间:1.092 ～ 15.932,1.232 ～21.622,1.190 ～5.254,P＜0.05).多因素Logistic回归分析发现miR-10b是急性胰腺炎PCD干预的独立影响因素(OR=2.374,95％可信区间:1.115 ～5.056,P＜0.05).结论 miR-10b与miR-146a可能成为判断急性重症胰腺炎严重程度的预测指标;miR-10b可能成为急性胰腺炎是否行PCD干预的判定指标.     

胰腺癌患者循环microRNA及吉西他滨耐药的胰腺癌患者特异性microRNA表达谱分析

目的 检测胰腺癌患者血浆中表达差异的microRNA及对吉西他滨耐药的胰腺癌患者血浆中表达差异的microRNA,为寻找新的生物标志物用于胰腺癌的无创性诊断及吉西他滨的疗效预测提供新的思路.方法 采用qPCR方法检测并筛选出胰腺癌患者血浆中相比于健康人表达差异明显的microRNA,以及对吉西他滨耐药的胰腺癌患者血浆中相比于对吉西他滨不耐药的胰腺癌患者表达差异明显的microR-NA.结果 胰腺癌患者相较于健康人存在表达差异的microRNA有28个,对吉西他滨耐药的胰腺癌患者相较于不耐药患者存在表达差异的microRNA有28个.结论 胰腺癌患者血浆中microRNA表达与正常人群有较显著的差异,胰腺癌患者中对吉西他滨耐药和不耐药者血浆microRNA也存在较显著差异,其有可能作为胰腺癌的诊断及疗效预测提供潜在的生物标志物.     

慢性不可预计温和应激大鼠microRNA差异表达谱分析

目的探讨慢性不可预计温和应激大鼠模型microRNA（miRNA）表达谱差异。方法采用慢性不可预计温和应激模型,将16只SD大鼠随机分为对照组和应激组,每组8只,对照组常规饲养,不予任何处理,应激组每天随机予1～2种温和刺激,共6周;造模结束后均采用旷场试验评价大鼠行为,安乐处死,取伏隔核低温保存。采用miRNA测序技术比较两组大鼠miRNA表达差异。结果与对照组比较,慢性不可预计温和应激大鼠有25个miRNA显著下调,2个miRNA显著上调。结论慢性不可预计温和应激可能使大鼠部分miRNA表达发生改变。     

New insight into the role of substance P/neurokinin-1 receptor system in breast cancer progression and its crosstalk with microRNAs

The neuropeptide substance P (SP) triggers a variety of tumor-promoting signaling pathways through the activation of neurokinin-1receptor (NK1R), a class of neurokinin G protein-coupled receptors superfamily. Recent researches in our and other laboratories have shown the overexpression of both SP and NK1R in breast cancer (BC) patients. SP/NK1R signaling is strongly implicated in the pathogenesis of BC through affecting cell proliferation, migration, metastasis, angiogenesis, and resistance. Therefore, SP/NK1R signaling responses must be rigorously regulated; otherwise, they would contribute to a more aggressive BC phenotype. Recently, microRNAs (miRNAs) as a specific class of epigenetic regulators have been shown to regulate NK1R and thus, controlling SP/NK1R signaling responses in BC. This review summarizes the current knowledge of the role of SP/NK1R signaling and its therapeutic potentials in BC. We also provide an overview regarding the effects of miRNA-mediated NK1R regulatory mechanisms in controlling BC tumorigenesis to gain a clearer view and thus better management of cancer.     

Sphingosine 1-phosphate/microRNA-1249-5p/MCP-1 axis is involved in macrophage-associated inflammation in fatty liver injury in mice

Monocyte chemotactic protein-1 (MCP-1) is one of the most representative inflammatory cytokines, and has been proved to be markedly increased in injured liver and sphingosine 1-phosphate (S1P)-treated macrophages. However, microRNAs (miRNAs) targeting MCP-1 and the role of miRNA/MCP-1 axis in S1P-mediated liver inflammation remain largely unknown. Here, we demonstrate that MCP-1 expression is increased in the liver and isolated liver macrophages of MCDHF mice. Moreover, there is a positive correlation between the hepatic levels of S1P and MCP-1. We then predict miRNAs targeting MCP-1 by bioinformatics analysis and select miRNA-1249-5p (miR-1249-5p) from the intersection of TargetScan database and downregulated miRNAs in the injured liver. S1P significantly upregulates the expression of MCP-1 and decreases miR-1249-5p expression in macrophages. MiR-1249-5p directly targets 3’-UTR of MCP-1 and negatively regulates its expression in S1P-treated macrophages. Administration of miR-1249-5p agomir decreases hepatic MCP-1 levels and attenuates liver inflammation in MCDHF mice. Protein-protein interaction network by STRING displays that S1P system is closely associated with MCP-1/CCR2 axis in the network of inflammation. In conclusion, we characterize the vital role of miR-1249-5p in negatively regulating MCP-1 expression in vitro and in vivo, which may open new perspectives for pharmacological treatment of liver disease.     

头颈部鳞状细胞癌预后相关的miRNAs的生物信息学分析

目的 利用癌症基因组图谱（TCGA）数据库微小核糖核酸（miRNAs）表达谱数据分析头颈部鳞状细胞癌（HNSCC）与癌旁正常组织间差异表达的miRNAs,结合临床信息寻找与HNSCC预后相关的miRNAs。方法 从TCGA中下载miRNAs表达数据,包括39例HNSCC患者和39个肿瘤邻近正常组织样本筛选差异表达的miRNAs,应用481例HNSCC患者的miRNAs表达谱和临床信息来评估找到的差异表达miRNAs的预后作用。结果 共筛选出114个差异表达的miRNAs,包括60个上调和54个下调的miRNAs。Kaplan-Meier生存分析显示miR-4652-5p和miR-99a-3p与HNSCC患者预后相关,单因素和多因素Cox回归分析显示,miR-4652-5p和miR-99a-3p是HNSCC的重要预后因素。结论 miR-4652-5p和miR-99a-3p与HNSCC患者预后相关,但miR-4652-5p和miR-99a-3p在头颈鳞状细胞癌发生发展中的分子机制仍需更全面的基础和临床研究进行探讨。