一个快速进化的microRNA家族

microRNAs(miRNAs)是长约22nt的非编码RNA,它可通过降解mRNA或抑制其翻译来调控基因。本文简要介绍了miRNAs的研究背景,阐述了通过比较近缘物种中非保守的miRNA基因来研究miRNAs分子进化的理由。我们的研究结果证实miRNA基因会受到达尔文正选择的影响,发生快速的进化。这一结果将为我们了解非蛋白编码基因的功能与进化提供崭新的视角。     

Noncoding RNAs: Different roles in tumorigenesis

A major portion of the mammalian genome is transcribed to produce large numbers of noncoding RNAs(ncRNAs).During the past decade,the discovery of small RNAs,including the microRNAs(miRNA) and small interfering RNAs(siRNA),has led to important advances in biology.The breadth of the ncRNA field of study has substantially expanded and many recent results have revealed a range of functions that can be attributed to the miRNAs and other ncRNAs.For example,H19 RNA,HOTAIR RNA,transcribed ultraconserved regions(T-UCRs),natural antisense RNA,transfer RNA and mitochondrial noncoding RNA have been suggested to play important roles in cancers and other diseases as well as in diverse cellular processes.In this review,we focus on the current status of several classes of ncRNAs associated with cancer with the emphasis on those that are not microRNAs.     

几种内源性小RNA的比较

RNA干涉是近年来的研究热点,广泛参与生物发育、细胞分化、细胞凋亡等多种生物学过程。本文综述了近年来对转录后靶基因调控的几种小RNA：siRNA、microRNA、piRNA和endo-siRNA,从特点、生物发生过程和生物学功能方面进行了综述性地比较,以期为进一步深入研究提供参考。     

水稻低温胁迫响应 ｍｉｃｒｏＲＮＡ 鉴定

水稻是世界三大粮食作物之一,然而低温胁迫会严重抑制水稻的生长发育。为了探究micoRNA在水稻低温胁迫中的作用,采用低温处理前,5℃低温处理24h和5℃低温处理48h的2~3叶期水稻整株,构建9个小RNA文库。通过高通量测序后,对9个小RNA文库的microRNA进行差异表达分析,一共筛选出21个与冷胁迫相关的microRNA,其中16个在冷胁迫下上调,5个在冷胁迫下下调。通过对这21个microRNA靶基因的CO富集结果表明,其靶基因广泛富集在包括信号转导,免疫系统和物质合成等细胞内过程中。这表明水稻可能通过多种micoRNA 介导,从各个方面来协同抵御低温胁迫。本研究为进一步阐明microRNA响应低温胁迫的分子机制提供了基础,且本研究所鉴定的microRNA为增强水稻对低温耐受性遗传改良提供了优异的miRNA资源。     

miRNA在人骨髓来源间充质干细胞成骨诱导分化过程中的表达

观察miRNAs在人骨髓来源间充质干细胞成骨诱导分化过程中的表达情况。以从骨髓中分离培养的MSCs及成骨诱导培养后的细胞为实验对象,利用基因芯片检测miRNAs的表达情况,由SAM分析得到MSCs较其诱导培养细胞中差异表达的miRNAs,再进行生物信息学分析。分离培养出的MSCs经成骨诱导培养14 d后,已具有成骨细胞特性;经芯片检测并SAM分析,成骨诱导培养的细胞较MSCs高表达的miRNAs有7个:hsa-miR-363*、hsa-miR-483、hsa-miR-590、hsa-miR-130a、hsa-miR-15b、hsa-miR-30c、hsa-miR-663;成骨诱导培养的细胞较MSCs低表达的miRNAs有6个:hsa-miR-192、hsa-miR-210、hsa-miR-128a、hsa-miR-224、hsa-miR-106a、hsa-miR-494。利用TargetScan预测其靶基因,并行生物信息学分析,其中hsa-miR-130a、hsa-miR-15b和hsa-miR-30c的预测靶基因多为维持干细胞特性的基因;而hsa-miR-106a和hsa-miR-494的预测靶基因多为参与骨形成及成骨分化的基因。为证明miRNAs参与调控MSCs的成骨分化过程提供了直接证据和研究基础。     

MicroRNA及其靶基因在糖尿病肾病小鼠肾脏的表达

 验证与糖尿病肾病小鼠肾脏相关的microRNAs的表达并运用实时荧光定量PCR分析靶基因与糖尿病肾病的关系。以db/db小鼠为模型组（DN组）,db/m小鼠为正常组（NC组）,定期测量小鼠的体重、血糖、甘油三酯、总胆固醇及24 h尿蛋白排泄率。留取DN小鼠与NC小鼠肾脏组织,检测肾脏组织形态学染色及实时荧光定量PCR（qRT-PCR）。qRT-PCR验证差异表达的microRNAs及其靶基因的mRNA表达水平。血糖、24 h尿蛋白排泄率结果表明糖尿病肾病动物模型构建成功。与NC小鼠相比,DN小鼠肾脏miR-196a、miR-21、miR-200b表达明显升高,且差异有统计学意义（P<0.05）。miR-196a、miR-200b、miR-21的表达水平与血糖、甘油三酯、总胆固醇、24 h尿蛋白排泄率存在正相关关系（P<0.05）。利用miRNAs数据库预测miR-196a的靶基因有ANX1、HOXB7、PTEN、FOXO1、HOXB8、HOXA5等。与NC组比较,DN组ANX1、FOXO1的mRNA表达水平降低,且差异有统计学意义（P<0.05）。同时ANX1、FOXO1与24 h尿蛋白排泄率存在正相关（P<0.05）。MiR-196a可能通过调节ANX1、FOXO1的表达水平来参与糖尿病肾病的发生发展。     

Early Diagnostic Value of Circulating MiRNA-21 in Lung Cancer： A Meta-Analysis

To evaluate the early diagnostic value of circulating miRNA-21 in diagnosis of lung cancer, databases such as Wan Fang, VIP, PubMed, and Elsevier were systematically searched from 2005 to 2013 to collect relevant references in which the diagnostic value had been evaluated. The statistics were consolidated and the qualities of the studies were classified. The data were analyzed using Meta Disc1.4 software. The diagnostic value of circulating miRNA-21 in lung cancer was assessed by pooling sensitivity, specificity, the likelihood ratio, and the Summary Receiver Operating Characteristic(SROC) curve. Publication biases of the studies involved were analyzed using Stata 11.0 software. A total of 143 papers were collected of which 8 were included, which contained 600 cases and440 controls. A heterogeneity test proved the existence of homogeneity in this study. Upon analysis using random effects models, the weighted sensitivity was 0.68, the specificity 0.77, the positive likelihood ratio 2.84, the negative likelihood ratio 0.40, and the SROC Area Under the Curve(AUC) was 0.8133. Further analysis by subgroup showed that the 5 indicators mentioned above were 0.72, 0.84, 4.50, 0.27, and 0.8987, respectively, for the serum group and 0.63, 0.70, 1.95, 0.53, and 0.7318, respectively, for the plasma group. We conclude that circulating miRNA-21can be regarded a valuable reference in diagnosis of lung cancer. This research showed that in lung cancer the early diagnostic value of miRNA-21 in serum was better than that in plasma.     

MicroRNA-25对大鼠骨关节炎软骨细胞增殖和凋亡调节作用

探讨miR-25对白细胞介素1β(IL-1β)促进OA软骨细胞凋亡和增殖的影响。以木瓜蛋白酶膝关节腔注射诱导骨性关节炎动物模型和SD大鼠骨性关节炎软骨细胞原代培养。IL-1β体外刺激OA软骨细胞,模拟骨性关节炎体外环境。MiR-25mimic或inhibitor转染至OA软骨细胞。利用Annexin V-FITC/PI和CCK-8法检测软骨细胞细胞凋亡和细胞增殖。miR-25过表达明显抑制软骨细胞凋亡而miR-25低表达促进软骨细胞凋亡(P0.05);miR-25 mimic促进软骨细胞增殖,而miR-25 inhibitor抑制软骨细胞增殖(P0.05)。miR-25介导OA发病发生,进展中发挥着保护性调节作用,抑制OA软骨细胞凋亡和促进其增殖作用,可能对OA发病机制有新的认识和提示OA新治疗策略。     

MicroRNA特征与功能

通过分析总结现代分子生物学国际前沿microRNA(miRNA)领域的研究文献，整理出miRNA研究的基本脉络和走向。miRNA是一类长度～22nt的非编码小分子RNA，在包括线虫、果绳、家鼠、人体以及拟南芥等生物中普遍存在；它在调节基因转录与表达，调控生物体正常发育等生理过程中扮演重要角色。从比较的角度出发，揭示了miRNA与小干扰RNA在其代谢与功能方面共用某些途径，相互交叉与替代，可能同属一个更广范围的小分子RNA介导的生理调控机制。miRNA的研究可能对新一代基因药物的开发具有深远意义。     

基于二硒化钼纳米球和杂交链式反应灵敏检测microRNA

利用SiO_2纳米球为模板水热法合成了二硒化钼纳米球,并以此材料为电极基底,电沉积上AuNPs后,进行交联链式反应进行信号放大,并结合过氧化物酶催化H_2O_2+HQ底液产生电化学信号高灵敏检测microRNA-21.结果表明:新方法在1.0×10~(-16)~1.0×10~(-10)mol/L的浓度范围内呈良好的线性关系,检出限为0.16fmol/L(R_(SN)=3).该传感器被成功应用于血清样品分析.