miRNAs在XIAP介导的乳腺癌细胞自噬和凋亡平衡性 调控中作用及其机制的研究

项目名称： miRNAs在XIAP介导的乳腺癌细胞自噬和凋亡平衡性 调控中作用及其机制的研究

项目编号： No.81472493

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 吴正升

作者单位： 安徽医科大学

项目金额： 80万元

中文摘要： 从理论角度，细胞自噬和凋亡属于两种不同的生物学进程，但在实际研究中，两者似乎又有着千丝万缕的联系，机制尚不明了。 研究前期发现：已知的凋亡抑制因子XIAP具有新的功能-参与细胞的自噬调控，提示其可能是自噬与凋亡对话的交点之一。那么XIAP在自噬和凋亡两种不同功能中如何平衡？对细胞行为有何影响？前期进一步以乳腺癌细胞为模型，通过芯片筛选并验证了两个调控XIAP的miRNAs，进一步发现这两个miRNAs对自噬和凋亡的调控具有截然不同的功能。据此推测：miRNAs可能在XIAP介导的自噬和凋亡功能的平衡性调控中发挥了作用。 为此，拟开展以下工作：①探索miRNAs参与XIAP介导的细胞自噬和凋亡调控平衡性的分子机制，验证该途径对乳腺癌化疗敏感性作用；②观察miRNAs-XIAP-自噬通路对乳腺癌细胞生物学行为的影响及机制。以期进一步认识自噬的调节机制及其与细胞凋亡之间的的关系。

中文关键词： C21_乳腺肿瘤；自噬；凋亡

英文摘要： Autophagy and apoptosis are different processes of cell activities. However, recent studies revealed that same genes and pathways were shared in progression of autophagy and apoptosis, suggesting that undefined connection may be involved in these processes. Our previous study demonstrated that X-linked inhibitor of apoptosis (XIAP), a well characterized regulator of apoptosis, had a novel role in autophagy inhibition among physiological and cancerous processes. Then, we would like to ask how XIAP balance these two functions of apoptosis and autophagy and what kind of effect was in the XIAP-regulated autophagy on cell behaviors. To investigate it, we further used the breast cancer cell as a model and scaned and then verified 2 miRNAs which specificly down-regulated XIAP expression. Intresetingly, we further revealed that differnt miRNAs which targets XIAP had different effects of apoptosis and autophagy induction. Thus, we presume that miRNAs might play important roles in the conversion of XIAP-regulated processes of autophagy and apoptosis, and then in the behavior of breast cancer cells. In this study, we will explore the molecular machnisms invovled the effects of anti-apoptosis and anti-autophagy of XIAP mediated by differet miRNAs.And we further investigate the role of this balance in the sensitivity of breast cancer chemotherapy. The other is investigating the impact of miRNAs-XIAP-autopthagy pathway in the behaviors of breast cancer cells and its mechanisam. From this study, we would like to somehow understand the regulation of autophagy and the relationship between autophagy and apoptosis.

英文关键词： breast cancer;autophagy;apoptosis