【摘要】：乳腺癌是全球女性發(fā)病率最高的惡性腫瘤。乳腺癌發(fā)生的分子機(jī)制目前并不十分清楚。PcG(Polycomb Group)蛋白作為基因表觀遺傳調(diào)控的抑制因子,廣泛存在于真核動(dòng)物細(xì)胞中。RYBP(Ring 1 and YY1 binding protein)是PcG家族成員之一,能與Ring1蛋白結(jié)合,自身泛素化并發(fā)揮E3泛素化連接酶的作用,繼而介導(dǎo)基因沉默。RYBP在調(diào)控基因表達(dá)、細(xì)胞功能等過(guò)程中起重要作用。已有研究證明,RYBP在多種腫瘤中異常表達(dá),顯示其與腫瘤存在一定相關(guān)性。本課題主要研究?jī)?nèi)容為RYBP在乳腺癌發(fā)生、發(fā)展中的作用及臨床意義、RYBP干預(yù)下的miRNA調(diào)控網(wǎng)絡(luò)構(gòu)建以及RYBP~miR-206~Nucleolin/VEGF通路在乳腺癌細(xì)胞中的調(diào)控機(jī)制。研究結(jié)果表明,與癌旁組織相比,RYBP在乳腺癌組織中異常高表達(dá),并與腫瘤惡性化程度存在明顯相關(guān)性;體內(nèi)、外實(shí)驗(yàn)證實(shí),RYBP在乳腺(癌)細(xì)胞增殖、遷移、侵襲、降低化療敏感性、維持干細(xì)胞特性等多種惡性表型中起促進(jìn)作用;通過(guò)miRNA芯片篩選發(fā)現(xiàn),RYBP在乳腺癌細(xì)胞中可調(diào)控多種與腫瘤密切相關(guān)的miRNA,并初步構(gòu)建了RYBP~miRNA~腫瘤信號(hào)通路/靶基因調(diào)控網(wǎng)絡(luò)。進(jìn)一步研究證實(shí),RYBP在乳腺癌細(xì)胞中與miR-206表達(dá)呈負(fù)相關(guān)性,并可通過(guò)RYBP~miR-206~Nucleolin/VEGF通路,調(diào)節(jié)乳腺癌細(xì)胞增殖及轉(zhuǎn)移。
[Abstract]:Breast cancer is the world's highest incidence of malignant tumors among women. The molecular mechanism of breast cancer is not well understood. PcG (Polycomb Group) protein, as the inhibitory factor of gene epigenetic regulation, is widely present in eukaryotic animal cells. RYBP (Ring 1 and YY1 binding protein) is a member of PcG family and can bind to Ring1 protein). Ubiquitin plays the role of E3 ubiquitin ligase and then mediates gene silencing. RYBP plays an important role in regulating gene expression and cell function. It has been proved that RYBP is expressed abnormally in many kinds of tumors, which indicates that RYBP is related to tumor. The main contents of this study are the role and clinical significance of RYBP in the occurrence and development of breast cancer and the construction of miRNA regulatory network under the intervention of RYBP and the regulation mechanism of RYBP~miR-206~Nucleolin/VEGF pathway in breast cancer cells. The results showed that the expression of RYBP in breast cancer was significantly higher than that in paracancerous tissues, and there was a significant correlation between RYBP and the degree of malignancy of breast cancer. In vivo and in vitro, it was confirmed that RYBP proliferates, migrates and invades breast (cancer) cells. Reducing chemosensitivity, maintaining stem cell characteristics and other malignant phenotypes play a role in promoting; It was found by miRNA microarray screening that RYBP could regulate many kinds of miRNAs closely related to tumor in breast cancer cells, and the RYBP signaling pathway / target gene regulatory network was preliminarily constructed. Further studies confirmed that RYBP has a negative correlation with miR-206 expression in breast cancer cells and can regulate the proliferation and metastasis of breast cancer cells through RYBP~miR-206~Nucleolin/VEGF pathway.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R737.9

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本文編號(hào)：2194750