天堂国产午夜亚洲专区-少妇人妻综合久久蜜臀-国产成人户外露出视频在线-国产91传媒一区二区三区

當(dāng)前位置:主頁 > 醫(yī)學(xué)論文 > 腫瘤論文 >

miR-155在結(jié)腸癌中的功能及作用機(jī)制的研究

發(fā)布時間:2018-07-08 10:46

  本文選題:miR-155 + HMG-box轉(zhuǎn)錄因子1(HBP1) ; 參考:《吉林大學(xué)》2016年博士論文


【摘要】:結(jié)腸癌是一種起源于大腸上皮組織的常見惡性腫瘤,發(fā)病率逐年增高,預(yù)后較差。研究發(fā)現(xiàn)mi RNA能夠在腫瘤中通過影響癌基因或者腫瘤抑制基因,發(fā)揮多種生物學(xué)功能。在正常情況下,癌癥中mi RNA的下調(diào)抑制原癌基因的表達(dá)。相反,也有腫瘤中高表達(dá)的mi RNA被發(fā)現(xiàn)并且抑制腫瘤抑制基因的表達(dá),因此mi RNA基因既可充當(dāng)腫瘤抑制基因又可充當(dāng)癌基因角色,基于mi RNA療法很可能轉(zhuǎn)化為一種有效的結(jié)腸癌治療策略。大量證據(jù)表明mi RNA如mi R-155與結(jié)腸癌病因?qū)W和生物學(xué)關(guān)系極其密切,而且mi R-155在多種腫瘤預(yù)防、診斷、治療及預(yù)后等臨床方面表現(xiàn)出良好的應(yīng)用前景。然而,mi R-155在結(jié)腸癌中作用的分子機(jī)制并不清楚。結(jié)腸癌中信號通路中最常見的改變是Wnt途徑的激活。Wnt/β-catenin信號通路在結(jié)腸癌早期發(fā)生中扮演重要角色。因此,本研究的目的是研究mi R-155在結(jié)腸癌中的功能及作用機(jī)制,探索mi R-155在結(jié)腸癌組織及細(xì)胞中的可能靶標(biāo)。方法:1.應(yīng)用實(shí)時熒光定量PCR和(或)Northern blot檢測結(jié)腸癌組織及細(xì)胞的mi R-155以及Wnt/β-catenin信號通路相關(guān)的靶基因Axin2,CD44和LGR5的表達(dá)水平。2.利用小鼠結(jié)腸癌異種移植瘤模型考察mi R-155對小鼠結(jié)腸癌腫瘤生長的影響。3.Western blot方法檢測細(xì)胞的增殖生物標(biāo)志物Ki-67,HBP1,β-catenin蛋白表達(dá)水平。4.利用TOPFlash報(bào)告基因檢測mi R-155對結(jié)腸癌細(xì)胞Wnt/β-catenin信號通路的影響。5.流式細(xì)胞儀檢測細(xì)胞周期,用Mod Fit軟件進(jìn)行細(xì)胞周期分析。6.MTT檢測細(xì)胞活性,計(jì)算細(xì)胞增殖率。7.利用生物信息學(xué)方法在線數(shù)據(jù)庫Target Scan(http://www.targetscan.org)對mi R-155可能的靶基因進(jìn)行預(yù)測。8.利用報(bào)告基因載體對mi R-155靶m RNA驗(yàn)證。9.斯皮爾曼分析方法分析mi R-155水平與結(jié)腸癌患者生存期相關(guān)性。結(jié)果:實(shí)時熒光定量PCR及Northern blot檢測發(fā)現(xiàn)與配對的癌旁正常結(jié)腸組織相比,結(jié)腸癌組織中mi R-155的表達(dá)水平顯著升高,結(jié)腸癌細(xì)胞系中mi R-155的表達(dá)水平較正常結(jié)腸上皮細(xì)胞系顯著升高。結(jié)腸癌細(xì)胞轉(zhuǎn)染mi R-155抑制劑后,增殖率顯著下降,并且阻斷Wnt/β-catenin信號通路。抑制mi R-155表達(dá)減慢小鼠結(jié)腸癌異種移植瘤的增長。生物信息學(xué)方法及報(bào)告基因載體確定HMG-box轉(zhuǎn)錄因子1(HBP1)為mi R-155新的靶分子,進(jìn)而介導(dǎo)Wnt/β-catenin信號通路。細(xì)胞轉(zhuǎn)染mi R-155抑制劑后抑制HBP1,β-catenin蛋白及Wnt/β-catenin信號通路相關(guān)的靶基因Axin2,CD44和LGR5的表達(dá)。另外,斯皮爾曼分析結(jié)果表明血清中高表達(dá)mi R-155結(jié)腸癌患者生存時間縮短。結(jié)論:mi R-155高表達(dá)可促進(jìn)結(jié)腸癌的腫瘤生長,它可能通過HBP1介導(dǎo)Wnt/β-catenin通路激活,參與腫瘤的發(fā)生發(fā)展過程。因此,mi R-155可能成為一種很有應(yīng)用前景的結(jié)腸癌臨床治療藥物。
[Abstract]:Colon cancer is a common malignant tumor originating from large intestine epithelium. The incidence of colon cancer is increasing year by year and the prognosis is poor. It has been found that mi RNA can play a variety of biological functions by influencing oncogene or tumor suppressor gene in tumor. Under normal conditions, the down-regulation of mi RNA inhibits the expression of proto-oncogenes in cancer. On the contrary, there are also high-expressed mi RNA in tumors that are found to inhibit the expression of tumor suppressor genes, so that mi RNA genes can act as both tumor suppressor genes and oncogenes Mi RNA-based therapy is likely to translate into an effective strategy for colon cancer treatment. A great deal of evidence shows that mi RNA, such as miR-155, is closely related to the etiology and biology of colon cancer, and miR-155 has a good prospect in the prevention, diagnosis, treatment and prognosis of many kinds of tumors. However, the molecular mechanism of the action of MMI R-155 in colon cancer is unclear. The most common change in the signaling pathway in colon cancer is the activation of the Wnt pathway. Wnt/ 尾 -catenin signaling pathway plays an important role in the early development of colon cancer. Therefore, the purpose of this study was to study the function and mechanism of miR-155 in colon cancer, and to explore the possible target of mi R-155 in colon cancer tissues and cells. Method 1: 1. Real-time fluorescent quantitative PCR and / or Northern blot were used to detect the expression levels of MIR-155 and Wnt- 尾 -catenin signaling pathway related target genes Axin2CD44 and LGR5 in colon cancer tissues and cells. The effect of miR-155 on tumor growth of mouse colon cancer xenografts was studied. 3. Western blot assay was used to detect the expression level of Ki-67 blot and 尾 -catenin protein. The effect of miR-155 on the Wnt- 尾 -catenin signaling pathway in colon cancer cells was detected by using Topflash reporter gene. Flow cytometry was used to detect cell cycle, cell cycle analysis was performed by Mod fit software. 6. MTT was used to detect cell activity and cell proliferation rate was calculated. Target scan (http://www.targetscan.org), an online database of bioinformatics, was used to predict the possible target gene of mi R-155. The reporter gene vector was used to validate the target mRNA of mi R-155. The correlation between MI-155 level and survival time of colon cancer patients was analyzed by Spelman analysis. Results: Real-time fluorescent quantitative PCR and Northern blot analysis showed that the expression level of mi R-155 in colon cancer tissues was significantly higher than that in matched adjacent normal colon tissues. The expression level of mi R 155 in colon cancer cell line was significantly higher than that in normal colon epithelial cell line. After transfection with mi R 155 inhibitor, the proliferation rate of colon cancer cells decreased significantly, and Wnt / 尾 -catenin signaling pathway was blocked. Inhibition of mi R 155 expression slowed down the growth of xenografts in mouse colon cancer. Bioinformatics method and reporter gene vector confirmed that HMG-box transcription factor 1 (HBP1) was a new target molecule of mi R-155, which mediated the Wnt- 尾 -catenin signaling pathway. The expression of HBP1, 尾 -catenin protein and the target genes axin2pCD44 and LGR5 related to Wnt- 尾 -catenin signaling pathway were inhibited after transfection of mi R-155 inhibitor. In addition, Spelman analysis showed that the survival time of colon cancer patients with high expression of mi R 155 was shortened. Conclusion the high expression of 1: mi R-155 can promote the growth of colon cancer. It may play an important role in tumorigenesis and progression through the activation of Wnt- 尾 -catenin pathway mediated by HBP1. Therefore, MMI R-155 may be a promising clinical therapy for colon cancer.
【學(xué)位授予單位】:吉林大學(xué)
【學(xué)位級別】:博士
【學(xué)位授予年份】:2016
【分類號】:R735.35

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 王毅;王芳;趙宏宇;王陽;周余來;原田守;山田亮;伊東恭悟;;前列腺酸性磷酸酶——結(jié)腸癌主動免疫治療新靶點(diǎn)[J];中國老年學(xué)雜志;2008年18期

2 邵世和,謝立蘋,霍龍;硒與結(jié)腸癌研究進(jìn)展[J];北華大學(xué)學(xué)報(bào)(自然科學(xué)版);2003年05期

3 程文芳,顧曉紅,錢偉,易粹瓊;結(jié)腸癌中腫瘤壞死因子相關(guān)凋亡誘導(dǎo)配體受體的表達(dá)[J];胃腸病學(xué);2003年02期

4 郭艷麗,閆慧明,宋善俊;組織因子在結(jié)腸癌表達(dá)的臨床意義(英文)[J];中國現(xiàn)代醫(yī)學(xué)雜志;2005年15期

5 李建國;王雙燕;沈若武;王守彪;;血管內(nèi)皮生長因子與結(jié)腸癌的相關(guān)性研究[J];山東醫(yī)藥;2006年07期

6 孫軍;沈磊;羅和生;沈志祥;;結(jié)腸癌瘦素和瘦素受體表達(dá)及其意義[J];中華消化雜志;2006年08期

7 宋e,

本文編號:2107178


資料下載
論文發(fā)表

本文鏈接:http://sikaile.net/yixuelunwen/zlx/2107178.html


Copyright(c)文論論文網(wǎng)All Rights Reserved | 網(wǎng)站地圖 |

版權(quán)申明:資料由用戶0210f***提供,本站僅收錄摘要或目錄,作者需要刪除請E-mail郵箱bigeng88@qq.com
日韩精品日韩激情日韩综合| 人妻乱近亲奸中文字幕| 免费精品一区二区三区| 国产精品激情在线观看| 亚洲第一区欧美日韩在线| 色丁香之五月婷婷开心| 日韩特级黄片免费观看| 日韩国产中文在线视频| 日韩国产亚洲欧美另类| 国产亚洲系列91精品| 色偷偷偷拍视频在线观看| 欧美日韩国产自拍亚洲| 午夜精品麻豆视频91| 欧美日韩精品视频在线| 小黄片大全欧美一区二区| 久久黄片免费播放大全| 亚洲精品伦理熟女国产一区二区| 人妻久久一区二区三区精品99| 亚洲国产性生活高潮免费视频| 日韩欧美三级视频在线| 久久精品亚洲精品一区| 国产精品蜜桃久久一区二区| 五月综合激情婷婷丁香| 久久99一本色道亚洲精品| 欧美成人一区二区三区在线| 久久re6热在线视频| 国产精品福利一级久久| 五月综合婷婷在线伊人| 极品少妇嫩草视频在线观看| 黄色国产一区二区三区| 亚洲国产中文字幕在线观看| 久久精品国产99精品最新| 东京热电东京热一区二区三区| 男女午夜在线免费观看视频| 欧美精品中文字幕亚洲| 免费特黄欧美亚洲黄片| 亚洲成人精品免费在线观看| 午夜福利国产精品不卡| 久久精品国产在热久久| 男人和女人干逼的视频| 91人妻人人澡人人人人精品|