RYBP在乳腺癌中的作用及相关miRNA调控机制研究
发布时间：2018-08-20 19:31
【摘要】：乳腺癌是全球女性发病率最高的恶性肿瘤。乳腺癌发生的分子机制目前并不十分清楚。PcG(Polycomb Group)蛋白作为基因表观遗传调控的抑制因子,广泛存在于真核动物细胞中。RYBP(Ring 1 and YY1 binding protein)是PcG家族成员之一,能与Ring1蛋白结合,自身泛素化并发挥E3泛素化连接酶的作用,继而介导基因沉默。RYBP在调控基因表达、细胞功能等过程中起重要作用。已有研究证明,RYBP在多种肿瘤中异常表达,显示其与肿瘤存在一定相关性。本课题主要研究内容为RYBP在乳腺癌发生、发展中的作用及临床意义、RYBP干预下的miRNA调控网络构建以及RYBP~miR-206~Nucleolin/VEGF通路在乳腺癌细胞中的调控机制。研究结果表明,与癌旁组织相比,RYBP在乳腺癌组织中异常高表达,并与肿瘤恶性化程度存在明显相关性;体内、外实验证实,RYBP在乳腺(癌)细胞增殖、迁移、侵袭、降低化疗敏感性、维持干细胞特性等多种恶性表型中起促进作用;通过miRNA芯片筛选发现,RYBP在乳腺癌细胞中可调控多种与肿瘤密切相关的miRNA,并初步构建了RYBP~miRNA~肿瘤信号通路/靶基因调控网络。进一步研究证实,RYBP在乳腺癌细胞中与miR-206表达呈负相关性,并可通过RYBP~miR-206~Nucleolin/VEGF通路,调节乳腺癌细胞增殖及转移。
[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.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.9
本文编号：2194750
[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.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.9
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