MicroRNA-532-5p Regulates Pericyte Function by Targeting the Transcription Regulator BACH1 and Angiopoietin-1

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Serum miRNA profiling identifies miR-150/30a as potential biomarker for workers with damaged nerve fibers from carbon disulfide

As crucial small regulatory molecules, serum microRNAs (miRNAs) have been widely identified as potential noninvasive biomarkers. To survey and identify serum miRNAs associated with workers who had experienced injury to their nerve system from carbon disulfide (CS₂), we profiled abnormally expressed miRNAs using the microarray technique and further performed qRT-PCR validation in case and control samples (n=20). Microarray profiling in pooled RNA samples showed that many miRNAs in workers exposed to CS₂ were aberrantly expressed. Based on control samples exposed to CS₂, a great amount of abnormal miRNAs, including some miRNA gene clusters and families, were obtained from microarray datasets. Most of deregulated miRNAs were up-regulated, and almost all miRNAs showed consistent expression patterns between workers with different numbers of damaged nerve fibers. Functional enrichment analysis suggested that these abnormal miRNAs showed versatile roles by contributing to multiple biological processes. Some aberrantly expressed miRNAs were characterized as miRNA gene clusters or families, and they always showed consistent expression patterns. miR-150 and miR-30a were selected to be further validated by qRT-PCR as up-regulated species, and they could discern case samples from control samples. miR-150 and miR-30a may be potential noninvasive biomarkers for a damaged nervous system.     

Influence of middle-distance running on muscular micro RNAs

A specific subset of micro RNAs (miRs), including miR-133 and miR-206, is specifically expressed in muscle tissue, so that they are currently defined as muscular miRs (myomiRs). To further elucidate the role of myomiRs in muscle biology, we measured miR-133a and miR-206 in plasma of 28 middle-age recreational athletes. The study population consisted of 28 middle aged, recreation athletes (11 women and 17 men; mean age, 46?years) who completed a 21.1?km, half-marathon. The plasma concentration of miR-133a and miR-206, the serum concentration of creatine kinase (CK) and high-sensitivity (HS) cardiac troponin T (cTnT), as well as capillary lactate, were measured before and immediately after the run. The median serum concentration of total CK (257 versus 175?U/L; p?p??4; p??4; p?=?.001) were considerably increased immediately after the half-marathon run. In multivariate analysis only post-exercise capillary lactate was found to be independently associated with running time. A significant and independent correlation was observed between plasma variations of the two miRs, but not with other physiological or laboratory parameters. The results of this study suggest that the biological significance of miR-133a and 206 variation after middle-distance running parallels but not overlaps the release of biomarkers of nonspecific tissue damage. Enhanced plasma values of these myomiRs may hence reflect a physiological response to high-intensity and/or prolonged exercise rather than tissue injury.     

慢性髓系白血病中let-7a-3甲基化态势及其临床意义

目的：探讨慢性髓系白血病（CM L ）患者中let‐7a‐3启动子的甲基化态势及其临床意义。方法建立实时定量甲基化特异性PCR （RQ‐MSP）分别检测25例对照者及52例CML患者骨髓单个核细胞中let‐7a‐3启动子未甲基化水平。结果52例CM L患者未甲基化let‐7a‐3启动子（59．6％）为阳性,而对照组仅1例（4％）阳性,两组比较差异有统计学意义（ P＜0．01）。ROC曲线分析表明,let‐7a‐3启动子未甲基化作为辅助诊断CM L有较好的特异性。未甲基化let‐7a‐3启动子水平与BCR／ABL融合基因转录水平呈显著正相关（ r＝0．641,P＝0．001）,但与患者的白细胞、血小板计数及血红蛋白水平无明显相关性（ P＞0．05）。在慢性期和加速期let‐7a‐3未甲基化水平显著高于急变期。结论 let‐7a‐3基因低甲基化水平随疾病进展而降低。     

CCl4诱导大鼠纤维化肝组织 microRNA 差异表达及其初步分析

目的：探索 microRNA 在四氯化碳(CCl4)诱导的大鼠纤维化肝组织中的差异表达及其意义。方法采用 microR-NA 高通量测序分析技术检测对照组(n=10)与模型组(n=10)肝脏组织 microRNA 表达,对差异 microRNA 进行靶基因预测,对靶基因进行基因本(GO)分析、pathway 分析。结果对照组与模型组间筛选出37个差异 microRNA,上调29个,下调8个;从microRNA-基因网络图中发现关键上调为 miR-184、miR-10b-5p、miR-199a-3p 等;关键下调为 miR-200b-3p、miR-199a-5p、miR-125b-5p 等。结论模型组 microRNA 表达谱变化明显,肝纤维化的形成与 microRNA 调控细胞增殖、凋亡、细胞周期等有关。     

Ⅳ和Ⅳ+Ⅴ型狼疮性肾炎患者血清microRNA标志物的芯片初筛?

目的：应用微小核糖核酸(microRNA)芯片技术初步筛选Ⅳ、Ⅳ+Ⅴ型狼疮性肾炎患者血清 microRNA,探讨血清microRNA在狼疮性肾炎病理分型中的作用。方法从北京大学深圳医院肾内科生物标本库中选取Ⅳ、Ⅳ+Ⅴ型狼疮性肾炎血清各4例,作为试验组;同时选取4例健康人血清作为对照组,使用 microRNA 芯片技术筛选差异表达的血清 microRNA。结果Ⅳ型和Ⅳ+Ⅴ型共有部分microRNA,其中22个有显著差异,Ⅳ型特异性microRNA有29个,Ⅳ+Ⅴ型特异性microRNA有3个。结论血清microRNA具有作为鉴别Ⅳ、Ⅳ+Ⅴ型狼疮性肾炎生物标志物的潜能。     

视网膜色素上皮细胞氧化应激相关microRNA的鉴定

目的：应用miRNA表达谱芯片筛选视网膜色素上皮细胞与氧化应激相关的miRNA,为更加全面深入地研究年龄相关性黄斑病变(age-related macular degeneration,AMD)发生的分子机制提供新的思路。

方法：培养D407细胞,分别使用100、200、400μmol/L H₂O₂处理细胞24h后,Trizol试剂抽提细胞总RNA,使用Exiqon miRCURY LNA^TM microRNA表达谱芯片(miRBase 16.0数据库)检测不同浓度处理后D407细胞miRNA的表达差异,并将不同浓度处理后的变化进行聚类分析。使用Stem loop realtime PCR对芯片结果进行验证,并运用生物信息学方法预测差异miRNA调控的靶基因。

结果：芯片所包含的1 425个已知miRNA中,共有367个在不同浓度H₂O₂处理后表达发生变化。通过Treeview软件进行聚类分析发现miR-31等17个miRNA随H₂O₂浓度的升高呈现逐渐降低的趋势,miR-206等7个则逐渐升高。PCR验证显示芯片结果准确性较好。

结论：H₂O₂作用前后RPE的miRNA表达存在明显差异,miRNA作为转录后水平的调节分子,参与了细胞氧化应激反应,可能在AMD的发生发展中起有重要作用。     

脂肪干细胞分化成血管内皮细胞前后miRNA的差异表达

目的：探讨人脂肪间充质干细胞向血管内皮细胞诱导分化前后microRNA （miRNA ）的差异表达,预测其靶基因。方法对人脂肪间充质干细胞诱导成的血管内皮细胞进行鉴定后,提取人脂肪间充质干细胞向血管内皮细胞诱导分化前后的 miRNA ,微阵列芯片检测表达谱的变化,对有显著差异的miRNA进行实时荧光定量PCR验证,通过TargetScan、Miranda、PITA 、RNAhybrid和microTar五个数据库预测靶基因。结果筛选、验证出四个显著差异表达的miRNA。其中,miR‐29b‐3p和miR‐5096为显著上调,miR‐143‐3p和 miR‐145‐5p为显著下调。预测到 OCT4、SOX2、KLF4、TGFB2、IGF1、TAF11、TMEM169、UHRF1和OSBPL6等相关靶基因。结论人脂肪间充质干细胞向血管内皮细胞诱导分化前后存在显著差异性表达的miRNA ,提示这些miRNA在其分化中有重要的调控作用。