医学数据挖掘 miRNA基础知识

1、microRNA non-coding RNA, ncRNA不能翻译成蛋白的功能性RNA分子Housekeeping non-coding RNAtRNAs、 rRNAs、snRNAs Regulatory non-coding RNAsmall non-coding RNAsiRNA、miRNA、piRNA etc.Long non-coding RNA （lncRNA，200 nt ）microRNA的概念microRNA简称miRNA，一类进化上保守的内源性的非编码RNA, 长度约22个核苷酸，在转录后层面调控基因的表达。非编码RNA约22调控基因的表达内源性转录后proteinmRNA

2、DNA功能表型转录后调控转录调控MicroRNA和其靶基因3非翻译区结合，导致RNA诱导的沉默复合体（RNA-induced silencing complex，简称RISC）降解其靶mRNA或阻碍其靶的翻译。miRNA的生物合成过程mature miRNAPrecursor miRNAPrimary miRNAmiRNA gene转录剪切剪切miRNA的生物合成过程70-90碱基22碱基几百几千碱基miRNA的一般特点序列特点非编码性成熟的miRNA 5 端为单一磷酸基团，3端为羟基,这一特点使它与大多数寡核苷酸和功能RNA 的降解片段区别开来；表达特点miRNA具有时序性以及组织特异性在特

3、定的时间，组织中才会表达保守型特点在物种间高度通过和靶基因3UTR（3非翻译区）结合导致RNA诱导的沉默复合体（RNA-induced silencing complex,简称RISC）降解其靶mRNA或阻碍其靶的翻译。miRNA的作用机制 RISC剖析重大疾病相关miRNA的调控机制和功能生物学证实Target genesmiRNA功能1功能n功能2表型It is clear that miRNAs have many different targets dozens in some cases, hundreds in others but depending on the cells i

4、nvolved, it seems likely that only a small number of them have a crucial role in cancer pathogenesis. nature reviews genetics (2009)microRNA靶基因预测算法原理miRNA“种子区”与mRNA的3UTR序列碱基互补第2-第8碱基miRNA与mRNA形成双链结构的热力学稳定性靶基因二级结构和靶点外序列对靶基因预测的影响靶点在多物种间的序列保守性基本步骤在3UTR上探寻和miRNA“种子区”完全互补的序列；计算miRNA和这些序列结合产生的自由能下降值，对靶点进行

5、筛选；对靶点进行物种间序列比对，利用物种保守性进一步筛选。miRNA靶位点预测的难点：miRNA与靶位点的不完全互不配对几种靶预测算法比较miRNAs regulate many key biological processes, by determining how and when genes turn on and off细胞的生长，增殖，分化，凋亡器官的建成生物个体的发育，繁殖与人类重大疾病相关Biological functions of miRNAs 基于mRNA、miRNA双重表达谱分析复杂疾病中的miRNA调控背景miRNAs influence cell proliferat

6、ion and tumorigenesis in a cell-type specific manner, depending on the milieu of target mRNAs that are expressed. It is clear that miRNAs have many different targets dozens in some cases, hundreds in others but depending on the cells involved, it seems likely that only a small number of them have a

7、crucial role in cancer pathogenesis. nature reviews genetics (2009)尽管差异表达分析方法已经识别了许多疾病miRNA，但是大部分miRNA在疾病中的作用还是未知的miRNAGene 1、Gene 2、Gene 3Gene 4、Gene N功能miRNA表达谱差异表达miRNA上调miRNA下调miRNAmRNA表达谱差异表达mRNA下调mRNA上调mRNA预测差异表达miRNA调控的靶基因预测的靶向关系GO功能注释/富集预测差异表达miRNA调控的靶基因数据mRNA表达谱miRNA表达谱miRNA-mRNA靶向关系皮尔森相关系数

8、注意：miRNA、mRNA表达谱中样本顺序要一致samplesexpressionmiRNAtargetmiRNAtargetAnti-correlation of microRNA expression and predicted target mRNA. Expression levels of miR-200c and VEGFA in the primary dataset showing anti-correlation in both ccRCC and matched normal kidney tissue.loss of miR-200c function in ccRCC

9、contributes to increase in VEGF levels.Case 1前提假设miRNAs implicated in a specific tumor phenotype will show aberrant regulation of their target genesA key difference from other methods is that we identified dysregulated network edges (regulations) instead of dysregulated nodes (miRNAs) to assemble di

10、sease-related signatures. IF：5.225in vitro analysis RDH11an oncogene, is located in a high-level amplifications region in tumor cells and specifically expressed in the prostate LRP1 promote the invasion and migration ability of lung cancer cells and glioblastoma cellsis directly regulated by hsa-miR-205 in lung cancer cells SMAD3, a major TGF- signaling transducer miRNA family 的协同失调作用包含三个miRNA家族mir-125, mir-181 和mir-145家族最小的后验概率为77.4% ，表明这些miRNA和前列腺癌相关这些基因富集的功能有pathways in prostat