本文選題：胃腺癌 + Nanog��； 參考：《河北大學(xué)》2017年碩士論文

【摘要】：胃癌是世界第二大致死惡性腫瘤,而其中胃腺癌又占95%以上。在中國,胃腺癌具有高發(fā)病率和高死亡率,病人的五年存活率非常低,因此胃腺癌是中國嚴(yán)重的公共衛(wèi)生問題,也是中國醫(yī)學(xué)急需解決的問題之一。本研究探究了 miR-199b-5p與干細(xì)胞標(biāo)志物Nanog及胃癌腫瘤干細(xì)胞標(biāo)志物CD44之間的關(guān)系,旨在深入了解miRNA對腫瘤以及腫瘤干細(xì)胞的調(diào)節(jié)作用,并且對胃腺癌腫瘤干細(xì)胞和腫瘤細(xì)胞進行轉(zhuǎn)錄組測序篩選出來差異表達(dá)的miRNA,為治療胃腺癌提供新的分子靶標(biāo)和研究思路。我們通過腫瘤細(xì)胞測序和生物信息學(xué)方法,預(yù)測出了 miR-199b-5p的靶向序列位于Nanog和CD44的3'UTR區(qū)域,可能存在抑制NANOG和CD44蛋白表達(dá)的情況。實驗部分主要通過在胃腺癌細(xì)胞系MGC803中過表達(dá)miR-199b-5p以觀察其對Nanog和CD44基因表達(dá)及蛋白翻譯水平的影響。結(jié)果說明miR-199b-5p對Nanog沒有影響,而CD44的表達(dá)在miR-199b-5p過表達(dá)的MGC803細(xì)胞中明顯降低,這一結(jié)果提示miR-199b-5p可抑制CD44基因的表達(dá)。通過在MGC803細(xì)胞中過表達(dá)miR-199b-5p,觀察miR-199b-5p對胃腺癌細(xì)胞生物學(xué)功能的影響。研究發(fā)現(xiàn),miR-199b-5p上調(diào)能顯著抑制胃腺癌細(xì)胞MGC803的增殖、遷移、侵襲及耐藥程度。這些實驗表明,miR-199b-5p可以作為抑癌基因,抑制腫瘤的發(fā)生、遷移、侵襲和耐藥。miR-199b-5p的細(xì)胞生物學(xué)作用可能與其抑制CD44相關(guān)。我們的結(jié)論是:miR-199b-5p是一個潛在的對腫瘤干細(xì)胞標(biāo)志物CD44具有調(diào)節(jié)作用的miRNA,通過抑制CD44從而抑制一系列腫瘤細(xì)胞生物學(xué)活性。這為胃腺癌腫瘤干細(xì)胞標(biāo)志物CD44信號通路的研究拓寬了基礎(chǔ),也為腫瘤的診斷和治療提供給了新的分子靶標(biāo)。然而,值得注意的是,miR-199b-5p在我們的實驗結(jié)果中表明可以抑制癌癥的發(fā)生和發(fā)展,但是我們通過smallRNA測序結(jié)果來看,miR-199b-5p在類腫瘤干細(xì)胞中的表達(dá)遠(yuǎn)遠(yuǎn)高于腫瘤細(xì)胞。我們目前只能猜測這與細(xì)胞對抗腫瘤的自救效應(yīng)或者ceRNA調(diào)控有關(guān),而進一步的研究需要通過實驗證實。
[Abstract]:Gastric cancer is the second leading malignant tumor in the world, in which gastric adenocarcinoma accounts for more than 95%. In China, gastric adenocarcinoma has a high incidence and high mortality, and the 5-year survival rate of patients is very low. Therefore, gastric adenocarcinoma is a serious public health problem in China and one of the urgent problems to be solved in Chinese medicine. This study explored the relationship between miR-199b-5p and stem cell marker Nanog and gastric cancer tumor stem cell marker CD44 in order to understand the regulatory effect of miRNA on tumor and tumor stem cells. The differentially expressed miRNAs were screened by transcriptome sequencing from gastric adenocarcinoma tumor stem cells and tumor cells, which provided a new molecular target and research idea for the treatment of gastric adenocarcinoma. By means of tumor cell sequencing and bioinformatics, we predicted that the target sequence of miR-199b-5p is located in the 3'UTR region of Nanog and CD44, which may inhibit the expression of NANOG and CD44. The effect of miR-199b-5p on the expression of Nanog and CD44 gene and protein translation was observed by overexpression of miR-199b-5p in gastric adenocarcinoma cell line MGC803. The results showed that miR-199b-5p had no effect on Nanog, but the expression of CD44 was significantly decreased in MGC803 cells with miR-199b-5p overexpression, which suggested that miR-199b-5p could inhibit the expression of CD44 gene. The effect of miR-199b-5p on the biological function of gastric adenocarcinoma cells was observed by overexpression of miR-199b-5pin MGC803 cells. It was found that the upregulation of miR-199b-5p could significantly inhibit the proliferation, migration, invasion and drug resistance of gastric adenocarcinoma cell line MGC803. These results suggest that miR-199b-5p may act as a tumor suppressor gene, inhibit tumorigenesis, migration, invasion and cell biology of drug-resistant .miR-199b-5p, and may be related to its inhibition of CD44. Our conclusion is that: miR-199b-5p is a potential regulator of CD44, a tumor stem cell marker, which inhibits the biological activity of a series of tumor cells by inhibiting CD44. The results provide a new molecular target for the diagnosis and treatment of gastric adenocarcinoma. However, it is worth noting that the expression of miR-199b-5p in tumor-like stem cells is much higher than that in tumor-like stem cells by smallRNA sequencing. We can only speculate that this is related to the cellular antitumor self-rescue effect or ceRNA regulation, and further research needs to be confirmed by experiments.
【學(xué)位授予單位】：河北大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R735.2

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