水牛泌乳期和非泌乳期miRNAs表达谱分析及miR-103和Novel-miR-57的靶向基因研究

发布时间：2018-07-12 12:03

  本文选题：水牛 + 泌乳期和非泌乳期　； 参考：《广西大学》2016年博士论文

【摘要】：奶水牛是热带亚热带地区重要的产奶动物,水牛奶占世界牛奶供给量的5%以上。水牛奶的乳脂率和乳蛋白含量是荷斯坦奶牛的2.22和1.72倍。因此,研究奶水牛泌乳生理的基因调控网络可以揭示奶水牛高营养形成的分子机制。MicroRNAs(miRs)是一类非编码的19-25nt的小RNA,通过与靶基因mRNA结合阻遏靶mRNA翻译或降解靶mRNA来调控蛋白的表达。据估算,30%的蛋白编码基因受到miR的调控。研究发现miRs在动物细胞分化、增殖和凋亡过程中发挥重要作用。成年动物乳腺组织可以经历细胞增殖、分化、去分化和凋亡的循环,是研究乳腺组织泌乳和生理的理想分子机制模型。对人和小鼠的研究结果表明人的乳腺特异性miRs有23个,而小鼠的乳腺特异性miRs只有9个,表明miRs在乳腺中发挥重要作用。目前研究主要是关于miRs在其他产奶家畜泌乳生理中的作用,水牛的泌乳期和非泌乳乳腺组织miRs表达谱尚无报导。本研究首次对水牛泌乳期和非泌乳期乳腺组织中miRs的表达谱和作用进行了研究,构建了奶水牛泌乳期和非泌乳期乳腺组织的miR表达谱,分析和验证了 18个miR的差异表达模式,对筛选出的差异显著表达bbu-miR-103和novel-miR-57及其靶向基因和功能进行了研究,以便为阐明奶水牛泌乳物质及能量代谢通路的分子作用机制奠定工作基础。1.水牛泌乳期和非泌乳期乳腺组织miRNA差异表达谱的构建及分析采集水牛泌乳高峰期和非泌乳期(干乳期)的乳腺样本,利用Solexa高通量测序技术构建了水牛泌乳期以及非泌乳期乳腺组织2个miRNA表达谱,获得非泌乳期和泌乳期18nt-31nt的12,569,467和12,768,110条高质量序列。统计显示,中国沼泽型水牛泌乳和非泌乳期的sRNA分布的宽度模式介于18-31nt之间,在22nt达到一个高峰值,其中泌乳期乳腺组织中22nt序列占总sRNA数量的33.4%。在miRbase17.0库中检测到成熟miRs和pre-miR分别是676个和662个,归属500个microRNA基因家族。本研究在水牛乳腺组织测序确认的成熟miRs和全部pre-miR分别为359个和363个,归属为259个miRs家族;从新发现的262个候选miR中鉴定出230个水牛新miRs,其中5个是水牛特有的miRs。对所有鉴定的miRNA的第一个核苷酸偏好性分析显示,U是19nt和25nt miRs的5'端最普遍的核苷酸(94.15%和97.90%)。统计其在染色体上的分布情况,发现68.77%的已知miR和84.69%的新miR位于常染色体上,成功定位于乳腺组织染色体上的基因间隔区。已知miR主要分布在21号和X染色体,分别为74和37个占总数量的635个的11.65%和5.83%。新发现的miR,在21号和X染色体上分别为38个和32个。总miR分布在常染色体和X染色体上,密度从0.09到1.05 miRs/Mbp不等。21号染色体是miRs主要表达的染色体,分布最多,总miRs,泌乳期表达miRs和非泌乳期miRs分别为1.05个/Mbp,1.34个/Mbp和1.35个/Mbp。泌乳期和非泌乳期miRs在相同染色体上的分布密度基本相同。2.水牛泌乳期和非泌乳期乳腺组织miRs差异表达谱分析在非泌乳期,bbu-miR-148a,bbu-let-7b,bbu-let-7a,bbu-miR-21,bbu-miR-143,bbu-miR-200c,bbu-miR-26a,bbu-miR-200a 和 bbu-let-7f 是主要表达 miRs,组成了 总已知miRNA序列的53.8%,每个miRs读数大于20,000个序列,表明它们是非泌乳期组织中高丰度表达miRs。在泌乳期发现有7个高表达的miRs(bbu-let-7b,bbu-let-7a,bbu-miR-26a,bbu-miR-125b,bbu-miR-21,bbu-miR-29a 和 bbu-let-7c),每个有 20,000 多条序列表达。比较两个样品组,bbu-miR-148a,bbu-miR-143,bbu-miR-200a,bbu-miR-141 和bbu-miR-30a-5p等这些miRs在泌乳期的表达量下降到非泌乳期的一半以下。而另外一些 miR,如 bbu-miR-26a,bbu-miR-29a,bbu-miR-125b,bbu-let-7c and bbu-miR-99a 在泌乳期比非泌乳期表现出多余或等于2倍序列丰度。根据KEGG对20个差异高表达miRNA的预测靶基因进行了功能分类。结果109个预测靶基因都被标记在MAPK信号通路,其他重要途径有Jak-STAT、催乳素(PRL)信号转导和胰岛素信号通路等。3.泌乳期和非泌乳期差异表达miRNAs筛选及QRT-PCR验证差异分析两个时期miRs的表达谱,筛选出18个miRs并运用QRT-PCR对其表达量进行验证。将其分为高丰度、低丰度和未知miRs:(a)9个高表达的已知的miR:bbu-miR-30a-5p,bbu-miR-141,bbu-miR-101,bbu-miR-103,bbu-miR-148a,bbu-miR-29a,bbu-miR-125b,bbu-miR-497 和 bbu-miR-125a;(b)4 个低丰度表达的 miR:bbu-miR-490,bbu-miR-217,bbu-miR-592 和 bbu-miR-2370*;(c)5 个高表达的未知 miR:novel-miR-57,novel-39,novel-148,novel-76 和 novel-123b。QRT-PCR 验证结果显示,bbu-miR-103,bbu-miR-125a、bbu-miR-30a-5p 和 bbu-miR-148a 在泌乳期表达量高于非泌乳期,其表达量分别为非泌乳期的2.43、3.43、4.06和5.29倍(P0.05);bbu-miR-29a在非泌乳期表达量为泌乳期的0.3倍,显著低于泌乳期(P0.05);bbu-miR-141,bbu-miR-125b,bbu-miR-497和bbu-miR-101的表达量在泌乳期高于非泌乳期,但差异不显著(P0.05)。低丰度的miR-490和miR-592在泌乳期表达量分别为非泌乳期的4.96和3.82倍,差异显著(P0.05)。在高丰度表达的5个的未知miRNA中,novel-39,novel-148,novel-76和novel-123b在泌乳期和非泌乳期差异不显著(P0.05),Novel-miR-57在泌乳期比非泌乳期高29.79倍(P0.05)。因此,选择miR-103和novel-miR-57作为下一步主要研究对象。4.Bbu-miR-103靶向基因PANK3调控乳脂代谢的研究基于人免疫缺陷慢病毒系统的载体骨架,构建了 LPEZX-PRE-MIR-103-1前体表达克隆载体(8219 bp),携带 Bbu-miR-103 前体序列。将 LPEZX-PRE-MIR-103-1 与对空载体LPEZX-MIR-NC分别与NRF和VSVG在293T细胞中进行包装和扩繁,获得了感染滴度分别为3.42×106 PFU/mL和3.47×106 PFU/mL的复制缺陷型病毒。用组织块法培养了乳腺上皮细胞,用等量对照和miR-103病毒原液感染乳腺上皮细胞48 h后,在显微镜下观察有绿色荧光蛋白发光,表明miR-103及空载对照病毒颗粒已经成功地进入了水牛乳腺上皮细胞中,代谢产生了过量miR-103。同时化学法合成miR抑制剂并进行转染试验。结果发现过表达和抑制表达miR-103与乳腺细胞靶基因PANK3表达呈现负相关。因此,推测PANK3是水牛miR-103作用的靶基因。过表达miR-103,下调了 PANK3的表达,显著提高了 SREBP1c和ACACA的表达。测定了过表达miR-103载体对水牛脂肪代谢通路8个关键的步骤相关基因的影响。结果发现,bbu-miR-103主要作用基因范围从脂肪酸从头合成开始、延伸至甘油三酯合成、乳脂合成和分泌以及脂肪酸吸收为止,对乳脂后续的转运代谢无较大影响。5.Novel-miR-57在Bcap-37和水牛乳腺上皮细胞上的靶基因—DOK4的狩猎及验证Novel-miR-57是在泌乳期和非泌乳期乳腺组织中筛选出的相对表达量差异最大的新发现miR,但在miRBase数据库检索不到类似或同族的miR。为此,我们运用MiRscan对Novel-miR-57的二级结构进行了预测。结果显示,Novel-miR-57可能有8个茎环结构,结合自由能为-28.0kcal/mol,Novel-miR-57的成熟序列位于miR的第一个茎环上。使用自编软件ensembl(v80)注释mRNA截取3'UTR,筛选结合自由能小于-20kcal/mol的mRNA 3'UTR与miR成熟序列的5'端的2-8种子序列进行配对,找到34个水牛转录组mRNA可能是Novel-miR-57的作用靶基因。这些基因包括CYP7B1、CACNG3、DOK4、COL17A1、和 ESN1 等基因,对这些基因进行了 GO assignment和KEGG信号通路预测分析。用水牛泌乳和非泌乳期乳腺组织cDNA添加线虫miR-39作为外参进行QRT-PCR定量分析,寻找差异表达靶基因。结果发现有6个基因检测不到,RCL1、UBE3C和NFRKB等10个基因在非泌乳期和泌乳期相对表达量相似或高于泌乳期;BRMSIL、ACTL8和ADORO等11个基因在泌乳期和非泌乳期相对表达量相似或高于非泌乳期;DLX3、CANCNG3、NFKBID、C17orf53、RTN1和FBXO10等7个基因在非泌乳期表达量远高于泌乳期,分别为128.03、144.23、146.24、160.96、160.38、274.40 和 326.24 倍,差异极显著(P0.01),可能为主要靶基因。化学合成Novel-miR-57的类似物Mimics和抑制剂Inhibitor,探讨Novel-miR-57的作用。结果发现,Bcap-37细胞系添加Novel-miR-57后能显著抑制DOK4基因的表达(P0.01),而Inhibitor能显著提高DOK4基因的表达(P0.01);而在水牛乳腺细胞添加100nM的Novel-miR-57后能显著促进DOK4基因的表达(P0.01),添加200nM的Inhibitor能显著抑制DOK4基因的表达(P0.01),与对Bcap-37细胞的作用相反。揭示了 DOK4是Novel-miR-57的作用靶基因,且Novel-miR-57能够根据不同细胞系不同生理条件来上调和下调DOK4基因的表达,最终对泌乳新陈代谢通路产生作用。结论:高差异表达Bbu-miR-103在水牛乳腺组织中的靶基因是PANK3。Bbu-miR-103通过从头合成途径促进脂肪酸合成,对水牛乳腺上皮细胞的甘油三脂合成、乳脂滴合成和分泌、脂肪酸激活等3个乳脂代谢步骤有促进作用。Novel-miR-57在Bcap-37细胞和水牛乳腺中的靶基因为DOK4,与水牛乳腺上皮细胞的分化有关。
[Abstract]:Milk buffalo is an important milking animal in tropical subtropical region. Milk and milk account for more than 5% of the world's milk supply. The milk fat rate and milk protein content are 2.22 and 1.72 times of Holstein cows. Therefore, the study of the molecular mechanism.MicroRNAs (miRs) of the high nutrition formation of milk and buffalo can be revealed by the study of the gene regulation network of milk buffalo lactating physiology. It is a small RNA of a class of non coded 19-25nt, which regulates protein expression by binding to target gene mRNA to inhibit target mRNA translation or degradation of target mRNA. It is estimated that 30% of the protein encoding gene is regulated by miR. Studies have found that miRs plays an important role in the process of differentiation, proliferation and apoptosis in animal cells. Adult mammary tissues can undergo fine experience. The cycle of cell proliferation, differentiation, dedifferentiation and apoptosis is an ideal molecular mechanism for the study of mammary tissue lactation and physiology. The results of human and mouse studies show that there are 23 human breast specific miRs and only 9 mammary specific miRs in mice, indicating that miRs plays an important role in the mammary gland. The present study is mainly about miRs in it The miRs expression profiles of the lactating and non lactation mammary tissues of buffalo were not reported. The expression and function of miRs in the lactation and non lactation tissues of buffalo were first studied for the first time. The miR expression profiles of milk buffalo lactation and non lactation mammary tissues were constructed and analyzed and verified. The differential expression patterns of 18 miR were used to express bbu-miR-103 and novel-miR-57 and their target genes and functions, so as to lay a work foundation for clarifying the molecular mechanism of lactating substance and energy metabolism pathway of milk Buffalo,.1. buffalo lactation and non lactating breast tissue miRNA differential expression profiles By constructing and analyzing mammary samples of buffalo lactation peak and non lactation period (dry milk period), 2 miRNA expression profiles of buffalo lactation and non lactation mammary tissues were constructed by Solexa high throughput sequencing technology, and 12569467 and 12768110 high quality sequences of 18nt-31nt in non lactation and lactation period were obtained. The width pattern of sRNA distribution in the lactation and non lactation period of the lustrate buffalo is between 18-31nt and a high peak in 22nt, of which the 22nt sequence of the mammary gland in the lactation period is 676 and 662 respectively, which belong to 500 microRNA gene families in the miRbase17.0 library, and belong to 500 microRNA genes. Bovine mammary gland tissue sequencing confirmed that mature miRs and total pre-miR were 359 and 363, belonging to 259 miRs families, and 230 New Buffalo miRs were identified from 262 newly found candidate miR, 5 of which were the first nucleotide bias analysis of all identified miRNA by Buffalo specific miRs., and U was the largest 5'end of 19nt and 25nt miRs. The common nucleotides (94.15% and 97.90%). The distribution of the chromosomes on the chromosomes shows that 68.77% of the known miR and 84.69% of the new miR are located on the autosomes, which are located successfully on the gene spacers on the chromosomes of the mammary tissues. The known miR is mainly distributed on the 21 and X chromosomes, divided into 74 and 37 of 635 of the total number of 11.65% and 5.83%.. The newly discovered miR was 38 and 32 on the 21 and X chromosomes. The total miR was distributed on the autosomes and the X chromosomes, and the density from 0.09 to 1.05 miRs/Mbp was the main chromosomes of miRs, the most distributed, the total miRs, the miRs and the non lactation miRs were 1.05 /Mbp, 1.34 /Mbp and 1.35 secreting periods. The distribution density of miRs on the same chromosome in milk and non lactation period was basically the same as that of.2. buffalo lactating and non lactating mammary gland tissue miRs differential expression profiles in non lactation period, bbu-miR-148a, bbu-let-7b, bbu-let-7a, bbu-miR-21, bbu-miR-143, bbu-miR-200c, bbu-miR-26a, bbu-miR-200a and bbu-let-7f were mainly expressed. 53.8% of the total known miRNA sequences, each miRs reading is greater than 20000 sequences, indicating that they are high abundance expression of miRs. in the non lactation period and found 7 high expression miRs (bbu-let-7b, bbu-let-7a, bbu-miR-26a, bbu-miR-125b, bbu-miR-21, bbu-miR-29a and bbu-let-7c) in lactation period, each of which has more than 20000 sequences. The two sample groups, such as bbu-miR-148a, bbu-miR-143, bbu-miR-200a, bbu-miR-141 and bbu-miR-30a-5p, decreased to less than half of the lactation period, and some other miR, such as bbu-miR-26a, bbu-miR-29a, bbu-miR-125b, bbu-let-7c and, showed excess or equal to 2 in lactation period than non lactation period. Sequence abundance. According to KEGG, the functional classification of the predicted target genes of 20 differentially expressed miRNA was carried out. Results 109 target genes were labeled in MAPK signaling pathway, other important pathways were Jak-STAT, PRL signal transduction and insulin signaling pathway and other.3. lactation and non lactation period differential expression miRNAs screening and QRT-PCR Verify the expression profile of miRs in the two period of difference analysis, select 18 miRs and verify its expression using QRT-PCR, and divide it into 9 known miR:bbu-miR-30a-5p, bbu-miR-141, bbu-miR-101, bbu-miR-103, bbu-miR-148a, bbu-miR-29a, bbu-miR-125b, bbu-miR-125b, and miRs:. 125A; (b) 4 low abundances of miR:bbu-miR-490, bbu-miR-217, bbu-miR-592 and bbu-miR-2370*; (c) 5 highly expressed unknown miR:novel-miR-57, novel-39, novel-148, novel-76 and novel-123b.QRT-PCR verification results showed that the expression level in lactation is higher than that of non lactation. The expression of bbu-miR-29a in non lactation period was 2.43,3.43,4.06 and 5.29 times (P0.05), and the expression of bbu-miR-29a in non lactation period was 0.3 times of lactation period, significantly lower than lactation period (P0.05); bbu-miR-141, bbu-miR-125b, bbu-miR-497 and bbu-miR-101 were higher than non lactation period in lactation period, but the difference was not significant (P0.05). MiR-490 and low abundance of miR-490 were not significant. The expression of miR-592 in lactation period was 4.96 and 3.82 times of non lactation period, respectively (P0.05). In 5 unknown miRNA with high abundance, novel-39, novel-148, novel-76 and novel-123b were not significantly different in lactation and non lactation period (P0.05), Novel-miR-57 was 29.79 times higher than non lactation period (P0.05). Therefore, select miR-103 And novel-miR-57 as the next major research object,.4.Bbu-miR-103 targeting gene PANK3 regulation of lipid metabolism, based on the carrier skeleton of the human immunodeficiency lentivirus system, constructed the LPEZX-PRE-MIR-103-1 precursor expression clone carrier (8219 BP), carrying the Bbu-miR-103 precursor sequence. LPEZX-PRE-MIR-103-1 and LPEZX-M to the empty body LPEZX-M. IR-NC was packed and expanded in 293T cells respectively with NRF and VSVG, and the infection titers were 3.42 * 106 PFU/mL and 3.47 * 106 PFU/mL respectively. The mammary epithelial cells were cultured by tissue block method. After infection of 48 h of mammary epithelial cells with equal control and miR-103 virus, the green fluores were observed under the microscope. Photoluminescence shows that miR-103 and unloaded control virus particles have been successfully entered into the buffalo mammary epithelial cells. Metabolic production of excessive miR-103. and chemical synthesis of miR inhibitors and transfection tests have been carried out. The results showed that overexpression and inhibition of expression of miR-103 were negatively correlated with the expression of PANK3 in mammary gland cells. Therefore, it was presumed that the expression of miR-103 was negatively correlated with the expression of PANK3 in the mammary gland cells. PANK3 is the target gene for the action of buffalo miR-103. Over expression of miR-103, down down the expression of PANK3 and significantly improving the expression of SREBP1c and ACACA. The effects of over expressed miR-103 vectors on the 8 key steps related genes of the buffalo fat metabolism pathway were determined. The results showed that the bbu-miR-103 main function gene range was synthesized from ab initio from fatty acids. Beginning, extending to triglyceride synthesis, milk fat synthesis and secretion, and fatty acid absorption, the hunt for the target gene of.5.Novel-miR-57 on Bcap-37 and buffalo mammary epithelial cells - the hunting and verifying that Novel-miR-57 is the relative expression of Novel-miR-57 in lactation and non lactation mammary tissues The new discovery miR has the largest difference in quantity, but we do not find similar or family miR. in the miRBase database. We use MiRscan to predict the two structure of Novel-miR-57. The result shows that Novel-miR-57 may have 8 stem ring structures, and the free energy is -28.0kcal/mol, and the mature sequence of Novel-miR-57 is located on the first stem ring of miR. Using the self-made software Ensembl (V80) annotation mRNA to intercept the 3'UTR and screen the 2-8 seed sequences of mRNA 3'UTR with the free energy less than -20kcal/mol and the 5'end of the mature miR sequence, and find that the mRNA of the 34 buffalo transcriptome may be the Novel-miR-57 target gene. These genes were predicted by GO assignment and KEGG signaling pathway. QRT-PCR quantitative analysis was carried out by adding nematode miR-39 in the breast tissue of buffalo and non lactation period cDNA to find the differential expression target gene. The results showed that 6 genes were not detected, and 10 genes such as RCL1, UBE3C and NFRKB were found in non lactation and lactation phases. The expressions of 11 genes, such as BRMSIL, ACTL8 and ADORO, were similar or higher than non lactation periods in lactation and non lactation periods, and 7 genes, such as DLX3, CANCNG3, NFKBID, C17orf53, RTN1 and FBXO10, were much higher in non lactation periods than in lactation period, which were 128.03144.23146.24160.96160.38274.40 and 326.2, respectively. 4 times, the difference is very significant (P0.01), may be the main target gene. Chemical synthesis of Novel-miR-57 analogues Mimics and inhibitor Inhibitor, to explore the role of Novel-miR-57. The results showed that the Bcap-37 cell line adding Novel-miR-57 can significantly inhibit the expression of DOK4 gene (P0.01), and Inhibitor can significantly increase the DOK4 gene expression (P0.01); and The addition of 100nM Novel-miR-57 to the buffalo mammary cells can significantly promote the expression of DOK4 gene (P0.01). The addition of 200nM Inhibitor can significantly inhibit the expression of the DOK4 gene (P0.01), which is contrary to the effect on Bcap-37 cells. It is revealed that DOK4 is the target gene of Novel-miR-57, and Novel-miR-57 can be based on different physiological conditions in different cell lines. To up-regulation and downregulate the expression of DOK4 gene and ultimately to the metabolic pathway of lactation. Conclusion: the target gene of high differential expression of Bbu-miR-103 in Buffalo mammary gland is that PANK3.Bbu-miR-103 promotes fatty acid synthesis through the ab initio pathway, glycerol three fat synthesis, lipid droplet synthesis and secretion, and fat drop in the mammary gland epithelial cells of Buffalo 3 lipid metabolism steps, such as acid activation, can promote the role of.Novel-miR-57 in the Bcap-37 cells and the buffalo mammary gland because of DOK4, which is related to the differentiation of the mammary epithelial cells of buffalo.
【学位授予单位】：广西大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：S823.83

【相似文献】

相关期刊论文 前10条

1 Wen Luo,;Qinghua Nie;Xiquan Zhang;;MicroRNAs Involved in Skeletal Muscle Differentiation[J];遗传学报;2013年03期

2 ;Small but influential:the role of microRNAs on gene regulatory network and 3′UTR evolution[J];遗传学报;2009年01期

3 B.SAILAJA;S.R.VOLETI;D.SUBRAHMANYAM;N.SARLA;V.VISHNU PRASANTH;V.P.BHADANA;S.K.MANGRAUTHIA;;Prediction and Expression Analysis of miRNAs Associated with Heat Stress in Oryza sativa[J];Rice Science;2014年01期

4 罗书芳;崔浪军;王健;屈生宪;;干旱胁迫下15种丹参miRNAs差异表达分析[J];广东农业科学;2013年05期

5 郝力力;李必富;;应用荧光定量PCR对细粒棘球绦虫miRNAs在虫体不同发育阶段表达量的研究[J];中国农学通报;2012年26期

6 Liming Ma;Lianghu Qu;;The Function of MicroRNAs in Renal Development and Pathophysiology[J];遗传学报;2013年04期

7 Gang Wu;;Plant MicroRNAs and Development[J];Journal of Genetics and Genomics;2013年05期

8 Xiang-Shun Cui;Xing-Hui Shen;Shao-Chen Sun;Sun-Wha Cho;Young-Tae Heo;Yong-Kook Kang;Teruhiko Wakayama;Nam-Hyung Kim;;Identifying MicroRNA and mRNA Expression Profiles in Embryonic Stem Cells Derived from Parthenogenetic,Androgenetic and Fertilized Blastocysts[J];遗传学报;2013年04期

9 叶瑞松;习欠云;束刚;王丽娜;王松波;朱晓彤;高萍;江青艳;张永亮;;GnRH引起猪垂体细胞miRNAs表达谱变化[J];畜牧与兽医;2012年S1期

10 陶新;徐子伟;;miRNAs对肠道健康的调控作用及机理[J];动物营养学报;2013年09期

相关会议论文 前10条

1 ;A potential role for Chlamydomonas miRNAs in response to environmental changes[A];中国遗传学会植物遗传和基因组学专业委员会2009年学术研讨会论文摘要汇编[C];2009年

2 Ping Xuan;Maozu Guo;Yangchao Huang;;MaturePred:Efficient Identification of MicroRNAs within Novel Plant Pre-miRNAs[A];第五届全国生物信息学与系统生物学学术大会论文集[C];2012年

3 Zhen-Dong Xiao;Li-Ting Diao;Jian-Hua Yang;Hui Xu;Mian-Bo Huang;Yong-Jin Deng;Hui Zhou;Liang-Hu Qu;;Systematical identification of cis-elements orchestrating the expressions of miRNAs in humans[A];生命的分子机器及其调控网络——2012年全国生物化学与分子生物学学术大会摘要集[C];2012年

4 ;Cell-free miRNAs may indicate diagnosis and docetaxel sensitivity of tumor cells in malignant effusions[A];2011医学科学前沿论坛第十二届全国肿瘤药理与化疗学术会议论文集[C];2011年

5 任波;马迪;李毅;;地高辛标记探针结合化学发光技术快速灵敏检测植物总RNA中的miRNAs方法[A];中国植物病理学会2005年学术年会暨植物病理学报创刊50周年纪念会论文摘要集[C];2005年

6 任波;马迪;李毅;;地高辛标记探针结合化学发光技术快速灵敏检测植物总RNA中的miRNAs方法[A];中国植物病理学会2005年学术年会暨植物病理学报创刊50周年纪念会论文集[C];2005年

7 戚鹏;韩金祥;鲁艳芹;王传玺;栾中华;卜范峰;;病毒编码的miRNAs:基因表达新的调控因子[A];山东省药学会2006年生化与生物技术药物学术研讨会论文集[C];2006年

8 ;Bioinformatic identification and expression analysis of new microRNAs from Medicago truncatula[A];华东六省一市生物化学与分子生物学会2008年学术交流会论文摘要汇编[C];2008年

9 ;Cell-free miRNAs may indicate diagnosis and docetaxel sensitivity of tumor cells in malignant effusions[A];中华医学会肿瘤学分会第七届全国中青年肿瘤学术会议——中华医学会肿瘤学分会“中华肿瘤 明日之星”大型评选活动暨中青年委员全国遴选论文汇编[C];2011年

10 ;miRNAs involved in Tau expression of BMSCs induced neurons[A];中国神经科学学会第九届全国学术会议暨第五次会员代表大会论文摘要集[C];2011年

相关重要报纸文章 前1条

1 江尚;特异性miRNAs与前列腺癌发病密切相关[N];中国医药报;2007年

相关博士学位论文 前10条

1 陈健德;新生儿脓毒症miRNAs表达谱及其免疫调节作用研究[D];复旦大学;2014年

2 A.B.M.Khaldun;[D];中国科学院研究生院(武汉植物园);2015年

3 成鹰;大肠杆菌和布鲁氏菌脂多糖刺激条件下巨噬细胞差异表达miRNAs的鉴定及其作用机制[D];海南大学;2014年

4 王奕;MiRNAs在白癜风外周血单个核细胞中的表达及miR-3940-5p对T细胞作用机制的研究[D];山东大学;2015年

5 陈科;小鼠子宫内膜mRNAs和miRNAs时空表达与胚胎着床的关系及SPOP对基质细胞蜕膜化的影响[D];重庆医科大学;2015年

6 侯冬霞;游离脂肪酸在脂肪组织胰岛素抵抗中的作用研究及Solexa技术在miRNAs检测中的应用研究[D];南京大学;2011年

7 李菁;分泌的miRNAs在2型糖尿病和血管再生中的生物学功能研究[D];南京大学;2011年

8 王凤;miRNAs对TBX5的靶向调控及其遗传变异的调控差异在先天性心脏病中的作用[D];复旦大学;2012年

9 周朝伟;猪不同年龄段肌肉组织microRNAs鉴定和差异表达分析[D];四川农业大学;2014年

10 陈键;模拟微重力下的血清miRNAs研究[D];浙江大学;2016年

相关硕士学位论文 前10条

1 姜青华;丹参miRNAs组织特异表达谱及其靶基因鉴定[D];杭州师范大学;2015年

2 刘元会;抑郁患者脑脊液和血清中差异性miRNAs鉴定的临床研究[D];四川医科大学;2015年

3 贾文慧;宫颈癌及子宫内膜癌血清miRNAs的研究[D];南京大学;2013年

4 许成辰;不同HER-2水平的人乳腺癌MCF-7细胞内miRNAs表达谱及相关miRNAs对癌细胞生物学行为的影响[D];安徽医科大学;2015年

5 曹文婷;奶山羊乳腺组织miRNAs的鉴定、筛选及功能的初步研究[D];西北农林科技大学;2015年

6 刘帅帅;循环miRNAs检测对肝癌诊断价值的meta分析[D];蚌埠医学院;2015年

7 王蕊;喉癌相关miRNAs的筛选及其功能的初步研究[D];南华大学;2015年

8 雷彬;大白猪和二花脸猪排卵前卵泡差异表达miRNAs及其靶基因鉴定[D];华中农业大学;2013年

9 葛莹;绵羊不同发情状态下松果体若干miRNAs表达差异及其与AANAT靶关系鉴定[D];扬州大学;2015年

10 汤自征;RA-FLS的迁移、侵袭及RA相关miRNAs表达水平的检测[D];扬州大学;2015年

，

本文编号：2117092