本文選題：食管鱗癌　切入點(diǎn)：miRNAs　出處：《昆明理工大學(xué)》2017年碩士論文

【摘要】：食管癌(EsophagealCarcinoma,EC)是最常見(jiàn)的消化道惡性腫瘤之一,其死亡率列惡性腫瘤第四位,5年生存率不到15%。在中國(guó),食管鱗狀細(xì)胞癌(Esophageal Squamous Cell Carcinoma,ESCC)是最主要的病理類(lèi)型,具有易復(fù)發(fā)和易轉(zhuǎn)移等特點(diǎn)。目前,手術(shù)切除和放化療是食管癌治療的主要方式,但由于食管癌在發(fā)病早期缺乏典型的臨床癥狀和有效的診斷技術(shù),食管癌發(fā)現(xiàn)時(shí)多數(shù)已經(jīng)處在中晚期,治療效果并不理想。因此,研究早期診斷食管癌的方法,并從分子水平探究食管癌的發(fā)生發(fā)展機(jī)制,對(duì)食管癌的早期診斷和治療具備重要意義。微小RNAs(miRNAs)是一類(lèi)內(nèi)源性的,長(zhǎng)度約為20-24個(gè)核苷酸的非編碼RNA,通過(guò)與靶基因的3' UTR區(qū)結(jié)合抑制基因轉(zhuǎn)錄后的翻譯和蛋白編碼基因的表達(dá)。miRNAs是在癌細(xì)胞的增殖、分化、衰老、凋亡和轉(zhuǎn)移等生物過(guò)程中發(fā)揮著重要作用。miRNAs在不同的惡性腫瘤中其生物學(xué)功能不同,最主要的原因是其調(diào)控的靶基因不同。不同的miRNAs可能調(diào)控著同一個(gè)靶基因,而一個(gè)miRNA可以調(diào)節(jié)許多不同的靶基因。miRNAs靶基因的預(yù)測(cè)是研究miRNAs作用機(jī)制的關(guān)鍵環(huán)節(jié)。因此,揭示腫瘤中差異表達(dá)的miRNAs與靶基因之間調(diào)控的關(guān)系是至關(guān)重要的。在論文中,我們深入研究了三個(gè)抑癌作用的miRNAs(miR-99a、miR-145和miR-125b)和一個(gè)具有致癌作用的miRNA(miR-1470)在食管癌變中的作用及其分子機(jī)制。首先通過(guò)miRNA表達(dá)譜芯片技術(shù)發(fā)現(xiàn)在食管鱗癌組織中miR-99a、miR-145和miR-125b表達(dá)顯著下調(diào);miR-1470在食管鱗癌組織中表達(dá)顯著上調(diào)。通過(guò)分析GEO-Dateset數(shù)據(jù)庫(kù),我們發(fā)現(xiàn)在GSE43732、GSE59973和GSE61047數(shù)據(jù)集中miR-99a、miR-145和miR-125b在食管鱗癌組織中表達(dá)同樣顯著下調(diào),這些數(shù)據(jù)進(jìn)一步驗(yàn)證了我們的芯片結(jié)果。接下來(lái)我們?cè)隗w外細(xì)胞模型中研究了miR-99a、miR-145和miR-125b在食管癌變過(guò)程中的作用,結(jié)果發(fā)現(xiàn)過(guò)表達(dá)miR-99a、miR-145和miR-125b可以顯著抑制食管鱗癌細(xì)胞的增殖、遷移和侵襲過(guò)程分子水平的研究進(jìn)一步發(fā)現(xiàn)miR-99a、miR-145和miR-125b通過(guò)調(diào)節(jié)細(xì)胞周期蛋白CCNA2、CCND1和CCNE1的mRNA水平從而抑制食管鱗癌細(xì)胞的增殖。miR-99a、miR-145和miR-125b通過(guò)調(diào)節(jié)Slug誘導(dǎo)的EMT和MMPs分子從而抑制食管鱗癌細(xì)胞的遷移和侵襲過(guò)程。miRNAs通過(guò)調(diào)節(jié)靶基因的3' UTR在腫瘤中發(fā)揮重要的功能。我們通過(guò)分子生物信息學(xué)數(shù)據(jù)庫(kù)并結(jié)合文獻(xiàn)報(bào)道發(fā)現(xiàn)miR-99a、miR-145和miR-125b通過(guò)各自的靶基因調(diào)控著腫瘤的惡性表型。我們發(fā)現(xiàn)miR-99a通過(guò)負(fù)調(diào)節(jié)靶基因IGF1R作用于食管鱗癌細(xì)胞增殖、遷移和侵襲過(guò)程。miR-145通過(guò)負(fù)調(diào)節(jié)靶基因SP1作用于食管鱗癌細(xì)胞增殖、衰老、遷移和侵襲過(guò)程。miR-125b通過(guò)負(fù)調(diào)節(jié)靶基因HMGA2作用于食管鱗癌細(xì)胞增殖、衰老、遷移和侵襲過(guò)程。本論文重點(diǎn)研究了食管鱗癌中差異表達(dá)miRNAs的致癌作用及其分子機(jī)制。通過(guò)本論文的研究將為揭示食管癌細(xì)胞增殖和侵襲運(yùn)動(dòng)的分子機(jī)制提供理論依據(jù),并為食管鱗癌的診斷和治療提供新型生物標(biāo)志物和治療靶點(diǎn)。
[Abstract]:Esophageal cancer (EsophagealCarcinoma, EC) is one of the most common malignant tumor of digestive tract, the mortality rate of malignant tumors among the fourth, 5 year survival rate is less than 15%. in Chinese, esophageal squamous cell carcinoma (Esophageal Squamous Cell Carcinoma, ESCC) is the main pathological type, with recurrence and metastasis characteristics at present. Surgical resection, and chemotherapy is the main treatment of esophageal cancer, but due to lack of typical clinical symptoms of esophageal carcinoma and effective diagnostic technique in the pathogenesis of early esophageal cancer, the majority found already in advanced treatment, the effect is not ideal. Therefore, the research method of early diagnosis of esophageal cancer, and to explore the mechanism of the occurrence and development of esophageal cancer at the molecular level, has important significance to the early diagnosis and treatment of esophageal carcinoma. Micro RNAs (miRNAs) is a class of endogenous, non RNA encoding length of about 20-24 nucleotides, with the target substrate Because the 3'UTR binding protein encoding gene translation and expression of.MiRNAs inhibit the post transcriptional gene is in cancer cell proliferation, differentiation, senescence, apoptosis and metastasis biology plays an important role in the process of.MiRNAs in different malignant tumor in its biological function, the main reason is the different target genes and its regulation the different miRNAs may regulate the same target gene prediction, and a miRNA can regulate many different target genes of.MiRNAs target genes is a key link to study the action mechanism of miRNAs. Therefore, the relationship between miRNAs and reveal the regulation of target gene expression in different tumors is very important. In this paper, we study three the role of tumor suppressor miRNAs (miR-99a, miR-145 and miR-125b) and has a carcinogenic effect of miRNA (miR-1470) and its role in molecular mechanism of esophageal carcinogenesis in the first through the miRNA. Microarray found miR-99a in esophageal squamous cell carcinoma, miR-145 and miR-125b expression were significantly reduced; significantly up-regulated expression of miR-1470 in esophageal squamous cell carcinoma. Through the analysis of the GEO-Dateset database, we found in GSE43732, GSE59973 and GSE61047 data from miR-99a, the expression of miR-145 and miR-125b in esophageal squamous cell carcinoma were also significantly reduced, these data further verified our microarray results. Then we studied the miR-99a in vitro cell model, the role of miR-145 and miR-125b in esophageal carcinogenesis. Results showed that over expression of miR-99a, miR-145 and miR-125b can significantly inhibit proliferation of esophageal squamous cell carcinoma cell proliferation, migration and invasion of molecular level further found that miR-99a, miR-145 and miR-125b by regulating cell cycle protein CCNA2, CCND1 and CCNE1 levels of mRNA and inhibit the cell proliferation of.M esophageal squamous cell carcinoma IR-99a, miR-145 and miR-125b by adjusting the EMT and MMPs molecules induced by Slug and inhibited.MiRNAs migration and invasion of esophageal squamous cell carcinoma cells play an important role in tumor by regulating target gene 3'UTR. We through molecular bioinformatics databases and literatures reported that miR-99a, miR-145 and miR-125b through the regulation of their target genes the malignant phenotype of tumor. We found miR-99a by negatively regulating the target gene of IGF1R in esophageal squamous cell carcinoma cell proliferation, migration and invasion of.MiR-145 through the negative regulation of target gene SP1 in esophageal squamous cell carcinoma cell proliferation, senescence, migration and invasion of.MiR-125b through the negative regulation of target gene HMGA2 in esophageal squamous cell carcinoma cell proliferation, migration and aging. The invasion process. This paper focuses on the study of the differences in expression of miRNAs esophageal squamous cell carcinogenesis and its molecular mechanism. Through this paper This study will provide a theoretical basis for revealing the molecular mechanism of esophageal cancer cell proliferation and invasion, and provide new biomarkers and therapeutic targets for the diagnosis and treatment of esophageal squamous cell carcinoma.

【學(xué)位授予單位】：昆明理工大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R735.1

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相關(guān)期刊論文 前3條

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本文編號(hào)：1663214