發(fā)布時間：2018-01-10 03:11

  本文關(guān)鍵詞：形覺剝奪性近視相關(guān)miRNA的生物信息學(xué)分析及功能預(yù)測　出處：《南京醫(yī)科大學(xué)》2017年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 形覺剝奪性近視 miRNA芯片 miRNA富集分析差異表達 miRNA靶標(biāo)預(yù)測和功能注釋

【摘要】：近視是影響全球的健康問題,根據(jù)資料推算,到2050年,全世界將有接近一半人口近視,并且全世界人口的1/10將會高度近視(高于600度近視)。在過去的幾十年中,近視發(fā)病率迅速增加,在很多東亞和東南亞國家的高中畢業(yè)生中近視發(fā)生率高達80%～90%,高度近視發(fā)生率達10～20%,已經(jīng)成為一個重大的公共健康問題。在世界其他地方,比如北美、歐洲和中東,盡管情況不如亞洲嚴(yán)重,但近視發(fā)病率也在逐年上升。雖然可以通過配戴眼鏡、隱形眼鏡或者進行屈光手術(shù)的方法矯正屈光不正,但由于篩查手段不健全、治療手段不實用或者缺乏經(jīng)濟能力等原因,近視仍然是目前視力損害的主要原因。此外,逐漸加深的近視還會增加視網(wǎng)膜脫離、白內(nèi)障、青光眼,甚至失明的風(fēng)險。對近視的有效預(yù)防和治療應(yīng)該建立在充分了解其發(fā)病機制的基礎(chǔ)之上。然而,盡管全球眾多學(xué)者多年來做了大量的研究,但是其具體發(fā)病機制至今仍不能明確。一般認為在形覺剝奪性近視(Form deprivation myopia,FDM)模型中主要通過兩種機制起作用,即"鞏膜主動重塑機制"和"局部視網(wǎng)膜調(diào)控機制",兩者均認為外界刺激作用于視網(wǎng)膜,啟動視網(wǎng)膜-視網(wǎng)膜色素上皮層-脈絡(luò)膜信號轉(zhuǎn)導(dǎo)系統(tǒng),把局部視網(wǎng)膜刺激信號轉(zhuǎn)化為調(diào)控鞏膜主動重塑的信號,誘導(dǎo)細胞外基質(zhì)表達異常,產(chǎn)生鞏膜膠原纖維改變等變化,引起鞏膜主動重塑,最終導(dǎo)致眼軸長度與屈光狀態(tài)不匹配,形成近視,引起視功能減退及各種并發(fā)癥。研究發(fā)現(xiàn),在鞏膜主動重塑過程中,miRNA起到重要信號傳導(dǎo)和調(diào)控作用。miRNA是一種小的非編碼單鏈RNA,在轉(zhuǎn)錄后水平上起著調(diào)控基因表達的重要作用。這種調(diào)控是通過與目標(biāo)基因3'非翻譯區(qū)(UTR)堿基配對的形式實現(xiàn)的,通過完美或近乎完美的配對(植物)或者不全配對(哺乳動物)產(chǎn)生翻譯抑制,導(dǎo)致mRNA裂解和降解。因此,miRNA可以作為信號網(wǎng)絡(luò)中的節(jié)點,通過調(diào)控基因表達量的變化,實現(xiàn)調(diào)節(jié)細胞的增殖、分化、代謝和凋亡等多種細胞活性的功能。目前已有大量研究報道m(xù)iRNA參與人體正常和疾病狀態(tài)過程,并在其中起到重要作用。研究發(fā)現(xiàn)眼部組織,如視網(wǎng)膜、晶狀體、角膜組織中均有miRNA的轉(zhuǎn)錄。只有極少數(shù)miRNA功能已知,而絕大多數(shù)miRNA在正常組織和疾病過程中的作用仍不明確。目前公認miRNA在非眼部和眼組織的正常生理和病理過程中起著至關(guān)重要的作用,以往研究發(fā)現(xiàn)在正常眼生長過程中(眼軸伸長),年輕且快速增長的眼球與那些成年穩(wěn)定(假定)的眼球鞏膜組織中的相關(guān)性miRNAs表達差異顯著。一些差異表達的miRNAs是活躍的鞏膜外細胞重塑和變薄的產(chǎn)物,可能與細胞外基質(zhì)重塑途徑有關(guān),從而使其成為預(yù)防或延緩近視進展的潛在靶點。作為探索潛在miRNA作為控制近視治療靶點的第一步,本研究試圖了解他們在近視發(fā)生過程中對鞏膜變化的作用,因為我們認為眼軸伸長(生長)形成近視的發(fā)展過程直接與鞏膜miRNA的差異調(diào)節(jié)有關(guān)。本研究以從已知的基因表達資料庫下載完整的配對良好的形覺剝奪性近視(FDM)小鼠模型miRNA芯片檢測數(shù)據(jù)為研究對象,采用生物信息學(xué)方法,探索與形覺剝奪性近視(FDM)高度相關(guān)的miRNA;再通過miRDB在線工具尋找與這些miRNA密切相關(guān)的基因;最后通過DAVID數(shù)據(jù)庫預(yù)測這此miRNA可能的功能。本研究旨在通過生物信息學(xué)方法尋找調(diào)控小鼠形覺剝奪性近視(FDM)發(fā)生發(fā)展過程的重要miRNA,預(yù)測其功能,為進一步實驗研究指明目標(biāo)和方向。本研究將從如下三部分分析形覺剝奪性近視(FDM)相關(guān)miRNA的生物學(xué)功能:第一部分形覺剝奪性近視相關(guān)miRNA生物信息學(xué)分析目的:探索和尋找與形覺剝奪性近視(FDM)形成過程密切相關(guān)的miRNA。方法:在公共基因芯片數(shù)據(jù)庫(Gene Expression Omnibus,GEO)中檢索并選取設(shè)計合理、資料完整的形覺剝奪性近視(FDM)小鼠模型相關(guān)miRNA芯片表達譜數(shù)據(jù)(GSE58124)。數(shù)據(jù)檢測組織為小鼠全眼組織、鞏膜組織和視網(wǎng)膜組織,同一小鼠右眼為實驗組,左眼為對照組,共納入樣本24個,6個全眼組織對照樣本、6個形覺剝奪性近視(FDM)全眼組織樣本;3個鞏膜組織對照樣本、3個形覺剝奪性近視(FDM)鞏膜組織樣本;3個視網(wǎng)膜組織對照樣本、3個形覺剝奪性近視(FDM)視網(wǎng)膜組織樣本。經(jīng)過數(shù)據(jù)預(yù)處理,使用中值法進行片間標(biāo)準(zhǔn)化,獲得單個數(shù)據(jù)矩陣的標(biāo)準(zhǔn)化后的矩陣。分別對三組配對的實驗組和對照組數(shù)據(jù)進行分析,取| logFC(FC,foldchange)|1且p0.05為入選標(biāo)準(zhǔn),篩選得到在形覺剝奪性近視(FDM)模型視網(wǎng)膜組織、全眼組織和鞏膜組織中有顯著差異的miRNA(上調(diào)或者下調(diào)),從中得到與形覺剝奪性近視(FDM)形成過程高度相關(guān)的miRNA。結(jié)果:經(jīng)過數(shù)據(jù)處理和分析,最終篩選得到視網(wǎng)膜組織中24個顯著差異miRNA(均為上調(diào))、全眼組織中20個顯著差異miRNA(均為上調(diào))、鞏膜組織中沒有符合條件的miRNA,經(jīng)過比對發(fā)現(xiàn)有8個miRNA在視網(wǎng)膜組織和全眼組織中均顯著上調(diào)。結(jié)論:至少有 8 個 miRNA(mmu-miR-468,mmu-miR-16-1*,mmu-miR-466h-5p,mmu-miR-466j,mmu-miR-669e,mmu-miR-15a*,mmu-miR-466c-5p-v15.0和mmu-miR-294)參與調(diào)節(jié)小鼠形覺剝奪性近視(FDM)形成過程。第二部分形覺剝奪性近視相關(guān)miRNA靶基因預(yù)測目的:預(yù)測8個共同差異表達的miRNA的下游調(diào)控靶基因。方法:運用在線數(shù)據(jù)庫軟件miRDB進行8個共同差異表達miRNA的下游調(diào)控靶基因預(yù)測。結(jié)果:經(jīng)過miRDB在線數(shù)據(jù)庫檢索,8個共同差異表達miRNA總共預(yù)測到1805個下游靶基因,其中2個靶基因被5個miRNA共同調(diào)控,5個靶基因被4個miRNA共同調(diào)控,82個靶基因被3個miRNA共同調(diào)控;共89個miRNA被至少三個miRNA共同調(diào)控。結(jié)論:7個至少被4個共同差異表達miRNA共同調(diào)控的靶基因分別為REEP3、MAPK10、INO80D、D630045J12RIK、FMR1、ARMC8 和 BACH2,它們可能是參與調(diào)控形覺剝奪性近視(FDM)的主要目的基因。第三部分形覺剝奪性近視相關(guān)miRNA功能預(yù)測目的:預(yù)測8個共同差異表達的miRNA的功能。方法:運用在線數(shù)據(jù)庫軟件 DAVID(The Database for Annotation,Visualization and Integrated Discovery)對8個共同差異表達miRNA預(yù)測的靶基因進行功能富集分析來研究差異表達miRNA的功能。結(jié)果:8個共同差異表達miRNA的靶基因通路富集分析結(jié)果發(fā)現(xiàn)在細胞通路層面上有5個miRNA的靶基因顯著的富集到了 mmu04360:Axon guidance通路(mmu-miR-16-1*、mmu-miR-294、mmu-miR-466c-5p、mmu-miR-466j 和 mmu-miR-468),4個miRNA 的靶基因顯著的富集到了 mmu04350:TGF-betasignaling pathway(mmu-miR-16-1*、mmu-miR-466j、mmu-miR-669e 和 mmu-miR-294)。在基因本體論層面上,GO:0045449～regulation of transcription被7個差異表達的miRNA 的靶基因所富集到,GO:0006350～transcription/GO:0006355～regulation of transcription,DNA-dependent/GO:0051252～regulation of RNA metabolic process 這4個GO BP條目被6個差異表達的miRNA的靶基因所共同富集到。mmu-miR-466h-5p與mmu-miR-466j的靶基因有非常多的共同富集到的GOBP條目,說明兩個 miRNA 之間的功能協(xié)作性。mmu-miR-294、mmu-miR-16-1*、mmu-miR-669e和mmu-miR-466c-5p這4個miRNA也有較多的功能協(xié)作。結(jié)論:8個共同差異表達的miRNA通過對靶基因的調(diào)控,干擾多個細胞通路或生物過程,從而在近視發(fā)展過程中發(fā)揮作用。結(jié)論1.miRNA或許并沒有在形覺剝奪性近視(FDM)小鼠的鞏膜組織中起到重要影響作用。2.在對全眼組織和視網(wǎng)膜組織的研究中發(fā)現(xiàn)8個顯著的共同表達上調(diào)的miRNA(mmu-miR-468,mmu-miR-16-1*,mmu-miR-466h-5p,mmu-miR-466j,mmu-miR-669e,mmu-miR-15a*,mmu-miR-466c-5p-v15.0 和 mmu-miR-294).3.miRNA 通過調(diào)控 REEP3、MAPK10、INO80D、D630045J12RIK、FMR1、ARMC8和BACH2等靶基因參與形覺剝奪性近視(FDM)的發(fā)展過程。4.通過對miRNA靶基因功能的預(yù)測分析顯示"轉(zhuǎn)錄調(diào)控"顯著增強,豐富了"軸突導(dǎo)向"和"TGF-β信號通路"被廣泛涉及,mir-466h-5p和mir-466j顯著富集在突觸傳遞相關(guān)的生物過程中。
[Abstract]:Myopia is a global health problem, according to the projections, by 2050, the world will have nearly half of the population of the world's population myopia, and high myopia (1/10 will be higher than 600 degrees of myopia). In the past few decades, the incidence rate of myopia increased rapidly in many East Asian and Southeast Asian countries in the high school graduates the incidence of myopia is as high as 80% to 90%, high myopia rate ranging from 10 to 20%, has become a major public health problem in the world. In other places, such as North America, Europe and the Middle East, although not in Asia but serious, the incidence of myopia is increasing year by year. Although you can wear glasses, contact lenses and methods or refractive surgery for correction of ametropia, but because screening is not perfect, treatment is not practical or lack of economic capacity and other reasons, myopia remains the leading cause of visual impairment. In addition, The deepening of myopia will increase retinal detachment, cataract, glaucoma, risk and even blindness. On the basis of effective prevention and treatment of myopia should be based on the full understanding of its pathogenesis. However, although many of the world's many years scholars have done a lot of research, but the mechanism is still not clear. In general form deprivation myopia (Form deprivation, myopia, FDM) mainly through two kinds of mechanisms in the model, namely "scleral remodeling mechanism" and "local retinal mechanism", both think outside stimulus effects on the retina, start the retina retinal pigment epithelium choroid to retina local signal transduction system. The stimulus signal into signal regulation in scleral remodeling, abnormal expression induced by extracellular matrix, produce scleral collagenous fibres change caused by changes in scleral remodeling The final result, axial length and refractive status does not match, the formation of myopia, visual hypofunction and various complications. The study found that in the process of scleral remodeling, miRNA plays an important role in signal transduction and regulation of.MiRNA is a small non encoding single stranded RNA, plays an important role in the regulation of gene expression in post transcriptional level. This regulation is through the target gene and 3'untranslated region (UTR) to realize the base pairing form, through perfect or near perfect pairing (plant) or incomplete pairing (mammalian) generated translation inhibition, leading to mRNA cleavage and degradation. Therefore, miRNA can be used as a signal node in the network, expression through the change of gene regulation, regulate cell proliferation, differentiation, metabolism and apoptosis of various cell activity functions. Many studies have reported miRNA in normal and disease of human body and in the process. Play an important role. The study found that the eye tissues, such as retina, lens, transcription of miRNA were in the corneal tissue. Only a handful of miRNA functions are known, and most of the miRNA function in normal tissues and disease are still not clear. The normal physiological and pathological processes as miRNA in non eye and eye tissue. Which plays a vital role in previous studies found in the normal eye growth process (axial elongation), young and the rapid growth of the eyeball and those of adult stable (assuming) miRNAs correlation of sclera tissue expression significant difference. Some differences between the expression of miRNAs is reshaping the scleral active cells and thinning of the product that may be associated with extracellular matrix remodeling pathway, which makes it a potential target to prevent or delay the progression of myopia. As the exploration potential miRNA as a first step to control myopia therapeutic targets, This study attempts to understand them in the process of the occurrence of myopia scleral changes, because we believe that the axial elongation (growth) during the formation and development of myopia and direct scleral miRNA differentially regulated. In this study, from the known gene expression database to download the complete good pairing of form deprivation myopia (FDM) mouse model miRNA microarray data as the research object, using bioinformatics methods, explore and form deprivation myopia (FDM) was highly correlated with miRNA; and then through the miRDB online tools to find those closely related to miRNA gene; finally through the DAVID database to predict the function of miRNA. This may be the purpose of this study is to search through bioinformatics methods control mice form deprivation myopia (FDM) is an important development of miRNA process, predict its function for further study indicates the target and direction. This research will be from the following The three part is the analysis of form deprivation myopia (FDM) related to the biological function of miRNA: in the first part of form deprivation myopia related bioinformatic analysis of miRNA Objective: To explore and find and form deprivation myopia (FDM) to form miRNA. process is closely related to the public: in the gene chip database (Gene Expression Omnibus, GEO) in the search and select the reasonable design, complete data form deprivation myopia (FDM) expression data related to mouse model of miRNA chip (GSE58124). Data organization for the detection mouse eye tissue, sclera and retina tissue, with a right mouse as the experimental group, the left eye as control group, were included in the sample 24, 6 full eye tissue control samples, 6 form deprivation myopia (FDM) ocular tissue samples; 3 scleral tissue control samples, 3 form deprivation myopia (FDM) the 3 kind of scleral tissue; retinal tissue control samples, 3 Form deprivation myopia (FDM) retinal tissue samples. After data preprocessing, chip standardization using median method, matrix single data matrix after standardization. Experimental group of three groups and paired control group data were analyzed from | logFC (FC, foldchange) |1 and P0.05 the inclusion criteria, screened in form deprivation myopia (FDM) retinal tissue model, there are significant differences of eye tissue and scleral tissue in miRNA (increasing or decreasing), and form deprivation myopia (FDM) formed from miRNA. results highly correlated process: after data processing and analysis, the final selection 24 significant differences in retinal tissue (miRNA were up-regulated), 20 significant differences miRNA ocular tissues (all up-regulated), scleral tissue did not meet the conditions for miRNA, after comparison found that 8 miRNA in the retina and ocular tissue Were upregulated. Conclusion: there are at least 8 miRNA (mmu-miR-468, mmu-miR-16-1*, mmu-miR-466h-5p, mmu-miR-466j, mmu-miR-669e, mmu-miR-15a*, mmu-miR-466c-5p-v15.0 and mmu-miR-294) were involved in the regulation of form deprivation myopia (FDM) formation process. The second part form deprivation myopia related miRNA target gene prediction to downstream target gene prediction expression 8 a common difference of miRNA. Methods: using online database software miRDB expression predicts downstream target gene miRNA 8 common difference. Results: after miRDB online database retrieval, miRNA a total of 1805 predicted target gene expression differences of 8 common, 2 of which target gene is 5 miRNA common control the 5 target gene is 4 miRNA regulated, 82 genes were 3 miRNA common control; a total of 89 miRNA was at least three miRNA common control. Conclusion: 7 by at least 4 The target gene miRNA to regulate expression of common differences were REEP3, MAPK10, INO80D, D630045J12RIK, FMR1, ARMC8 and BACH2, they may be involved in the regulation of form deprivation myopia (FDM) gene. The third part is the main purpose of form deprivation myopia related miRNA function prediction Objective: to predict the expression of 8 common difference the function of miRNA. Methods: using online database software DAVID (The Database for Annotation Visualization and Integrated Discovery) expression of functional enrichment analysis to study the differential expression of miRNA function of the miRNA target gene prediction of 8 common differences. Results: the target miRNA gene pathway enrichment analysis showed that the target gene has 5 miRNA in cells the level of significant enrichment pathway to mmu04360:Axon guidance pathway 8 common difference (mmu-miR-16-1*, mmu-miR-294, mmu-miR-466c-5p, mmu-miR-466j and mmu- MiR-468), the target gene 4 miRNA significant enrichment to mmu04350:TGF-betasignaling pathway (mmu-miR-16-1*, mmu-miR-466j, mmu-miR-669e and mmu-miR-294). The gene ontology level, GO:0045449 ~ regulation of transcription is the target gene 7 differentially expressed by miRNA enrichment, GO:0006350 ~ transcription/GO:0006355 ~ regulation ~ of transcription, DNA-dependent/GO:0051252 regulation of RNA metabolic process 4 GO BP entries were target genes of 6 differentially expressed miRNA common enrichment to target genes.Mmu-miR-466h-5p and mmu-miR-466j have a lot of common enrichment to GOBP entries, that function collaboration between two miRNA.Mmu-miR-294, mmu-miR-16-1*, mmu-miR-669e and mmu-miR-466c-5p 4 miRNA also has the function of collaboration more. Conclusion: the expression of 8 common differential miRNA through the target Gene regulation, interference of multiple cell signaling or biological process, which play a role in the development of myopia in the process. Conclusion 1.miRNA may not in form deprivation myopia (FDM) plays an important role in.2. found 8 significant co expression upregulation of miRNA in the study of the whole eye tissue and retinal tissue to tissue sclera in mice (mmu-miR-468, mmu-miR-16-1*, mmu-miR-466h-5p, mmu-miR-466j, mmu-miR-669e, mmu-miR-15a*, mmu-miR-466c-5p-v15.0 and mmu-miR-294) of.3.miRNA MAPK10, through regulating REEP3, INO80D, D630045J12RIK, FMR1, ARMC8 and BACH2 target genes involved in form deprivation myopia (FDM) in the development process of.4. through the prediction of miRNA target gene function analysis showed that "transcriptional regulation" was significantly enhanced and enriched "axon guidance" and "TGF- beta signaling pathway is widely involved, mir-466h-5p and mir-466j were significantly enriched in synaptic transmission. In the biological process of closing.

【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R778.11

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8 閆磐石;張金嵩;郭浩軼;;轉(zhuǎn)化生長因子-β_2在豚鼠形覺剝奪性近視中的表達[J];眼科研究;2007年03期

9 李秀娟;張金嵩;;形覺剝奪性近視雛雞眼細胞凋亡情況觀察[J];鄭州大學(xué)學(xué)報(醫(yī)學(xué)版);2008年06期

10 王應(yīng)飛;張金嵩;;神經(jīng)生長因子在豚鼠形覺剝奪性近視中的作用[J];醫(yī)藥論壇雜志;2010年21期

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