本文選題：膀胱癌 + 長(zhǎng)鏈非編碼RNA��； 參考：《中國(guó)人民解放軍醫(yī)學(xué)院》2017年碩士論文

【摘要】：背景膀胱癌是泌尿系統(tǒng)最常見(jiàn)的腫瘤,在其發(fā)生發(fā)展過(guò)程中,腫瘤侵襲起著重要的作用,根據(jù)腫瘤侵襲程度的不同,膀胱癌又被分為非肌層浸潤(rùn)型膀胱癌(non-muscle invasive bladder cancer, NMIBC)及肌層浸潤(rùn)型(muscle invasive bladder cancer, MIBC),其中,MIBC惡性程度高,復(fù)發(fā)率高,預(yù)后較差,死亡率明顯高于NMIBC。近年來(lái),雖然相關(guān)診療手段有了較大提高,但臨床確診膀胱癌仍然依靠有創(chuàng)性的膀胱鏡檢,這對(duì)早起篩查膀胱癌造成了不利影響,因此,深入探討研究膀胱癌病因?qū)W相關(guān)機(jī)制,具有重要的臨床意義。長(zhǎng)鏈非編碼RNA(Long-noncoding RNA, LncRNA)是一類長(zhǎng)度超過(guò)200個(gè)nt,但沒(méi)有編碼蛋白質(zhì)的一類RNA,占人體RNA總數(shù)的80%以上,LncRNA與腫瘤的相關(guān)研究是近年來(lái)的熱點(diǎn),包括多種LncRNA被認(rèn)為在胃癌、前列腺癌、乳腺癌、肺癌、膀胱癌等惡性腫瘤中表達(dá)水平發(fā)生顯著改變,但缺乏相關(guān)機(jī)制研究。方法通過(guò)基因芯片對(duì)膀胱癌及癌旁組織差異表達(dá)的LncRNA進(jìn)行分析,選取其中表達(dá)差異顯著的LncRNA,利用實(shí)時(shí)定量PCR技術(shù)(qPCR)進(jìn)一步篩選,接著在34例患者中進(jìn)行驗(yàn)證,在此基礎(chǔ)上對(duì)LncRNA表達(dá)水平與膀胱癌患者臨床指標(biāo)進(jìn)行關(guān)聯(lián)性分析。構(gòu)建過(guò)表達(dá)NONHSAT070806載體,將其瞬時(shí)轉(zhuǎn)染入膀胱癌細(xì)胞T24和5637中,檢測(cè)細(xì)胞過(guò)表達(dá)NONHSAT070806后凋亡、增殖、侵襲、遷移和克隆形成能力的變化,探討NONHSAT070806在體外對(duì)膀胱癌細(xì)胞生物學(xué)特性的影響。更進(jìn)一步,將轉(zhuǎn)染NONSHAT070806過(guò)表達(dá)載體和對(duì)照空白載體的5637細(xì)胞注射入裸鼠皮下,構(gòu)建裸鼠成瘤模型,通過(guò)測(cè)量瘤體體積和重量,分析NONHSAT070806對(duì)膀胱癌細(xì)胞體內(nèi)成瘤能力的影響。結(jié)果發(fā)現(xiàn)正義鏈長(zhǎng)鏈非編碼RNANONHSAT070806在大部分患者膀胱癌組織中表達(dá)水平下降(24/34, 70.6%),且其表達(dá)水平與患者腫瘤侵襲程度呈負(fù)相關(guān)(p0.05),而與其他臨床指標(biāo),如年齡、性別、吸煙史無(wú)統(tǒng)計(jì)學(xué)相關(guān)性。細(xì)胞功能學(xué)實(shí)驗(yàn)結(jié)果表明,NONHSAT070806過(guò)表達(dá)后,可誘導(dǎo)細(xì)胞凋亡,抑制細(xì)胞增殖、遷移、侵襲和細(xì)胞克隆形成能力(p0.05 ),動(dòng)物實(shí)驗(yàn)結(jié)果同樣表明,NONHSAT070806過(guò)表達(dá)可以在體內(nèi)抑制膀胱癌細(xì)胞成瘤能力(p0.05)。結(jié)論NONHSAT070806在膀胱癌中低表達(dá),且其表達(dá)水平與腫瘤侵襲有關(guān),其可能通過(guò)抑制膀胱癌侵襲發(fā)揮其抑癌作用,下一步關(guān)于其作用靶點(diǎn)及相關(guān)機(jī)制的研究將有助于揭示膀胱癌的發(fā)病機(jī)制。
[Abstract]:Background bladder cancer is the most common tumor in the urinary system. Tumor invasion plays an important role in the process of its occurrence and development, according to the degree of tumor invasion. Bladder cancer was also divided into non-muscle invasive bladder cancer, (non-muscle invasive bladder cancer,) and muscle invasive bladder cancer, (invasive bladder cancer,), in which the malignant degree, recurrence rate and prognosis were higher, and the mortality was significantly higher than that of NMIBC. In recent years, although the methods of diagnosis and treatment have been greatly improved, the clinical diagnosis of bladder cancer still depends on invasive cystoscopy, which has a negative impact on early screening of bladder cancer. It has important clinical significance. Long-noncoding RNAs (LncRNAs) are a class of RNAs with length of more than 200 nts but no coding proteins, which account for more than 80% of the total RNA of human body. The research on the relationship between LncRNA and tumors has been a hot topic in recent years, including many kinds of LncRNAs are considered to be involved in gastric cancer and prostate cancer. The expression level of breast cancer, lung cancer, bladder cancer and other malignant tumors have changed significantly, but lack of related mechanism. Methods the differentially expressed LncRNAs in bladder cancer and its adjacent tissues were analyzed by gene microarray. LncRNAs with significant difference in expression were selected and further screened by real-time quantitative PCR, and then verified in 34 patients. On this basis, the correlation between the expression of LncRNA and the clinical indexes of bladder cancer was analyzed. Overexpression of NONHSAT070806 was constructed, and its transient transfection into bladder cancer cells T24 and 5637 was used to detect the changes of apoptosis, proliferation, invasion, migration and clone formation after overexpression of NONHSAT070806. To investigate the effect of NONHSAT070806 on the biological characteristics of bladder cancer cells in vitro. Furthermore, 5637 cells transfected with over expression vector of NONSHAT070806 and control vector were injected subcutaneously into nude mice to construct tumor-forming model of nude mice. The effect of NONHSAT070806 on the tumorigenesis of bladder cancer cells was analyzed by measuring the volume and weight of tumor. The results showed that the expression level of NONHSAT070806 in most patients with bladder cancer decreased by 24 / 34,70.660. The expression level of NONHSAT070806 was negatively correlated with the degree of tumor invasion, but with other clinical parameters, such as age, sex, etc. There was no statistical correlation in smoking history. The results of cell function test showed that the overexpression of NONHSAT070806 could induce cell apoptosis, inhibit cell proliferation and migration. The results of animal experiments also showed that the overexpression of NONHSAT070806 could inhibit the tumorigenesis ability of bladder cancer cells in vivo. Conclusion the expression of NONHSAT070806 is low in bladder cancer, and its expression level is related to tumor invasion, which may play a role in inhibiting the invasion of bladder cancer. Further studies on its target and related mechanisms will be helpful to reveal the pathogenesis of bladder cancer.
【學(xué)位授予單位】：中國(guó)人民解放軍醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R737.14

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