线粒体融合基因2（MFN2）与骨肉瘤的相关性及其分子机制的研究

发布时间：2018-06-04 00:34

本文选题：骨肉瘤 + 线粒体融合基因2　；参考：《三峡大学》2016年硕士论文

【摘要】：目的:线粒体融合基因2(MFN2)的抑癌作用虽在许多肿瘤中被证实,其在肿瘤发生发展中机制却鲜有报道。本研究拟揭示MFN2与骨肉瘤的相关性及机制。方法:(1)收集骨肉瘤标本,分析MFN2表达及与生存的关系;(2)构建MFN2过表达的慢病毒,感染MG63和U2OS细胞,探究MFN2表达上调对骨肉瘤细胞增殖和凋亡等的影响;(3)纯化FLAG-MFN2蛋白诉诸质谱分析,IP验证相互作用;(4)CRISPR/cas9敲除/低U2OS的MFN2;(5)研究MFN2与骨肉瘤的相关性及机制。结果:(1)骨肉瘤组织中MFN2表达低于瘤旁,其水平与生存率正相关;(2)筛选出病毒感染的细胞,证实MFN2对骨肉瘤的抑癌作用;(3)首次发现MFN2与PLK1的相互作用;(4)CRISPR/cas9技术下调MFN2;(5)U2OS中MFN2与PLK1表达反相关;结论:MFN2是一种新的骨肉瘤抑癌基因,其抑癌作用与负向调控PLK1相关。靶向MFN2/PLK1轴有望成为骨肉瘤精准医学的新思路。
[Abstract]:Objective: although the inhibitory effect of mitochondrial fusion gene (mtm2MFN2) has been confirmed in many tumors, its mechanism in tumorigenesis and development is rarely reported. This study is intended to reveal the correlation and mechanism between MFN2 and osteosarcoma. Methods Osteosarcoma specimens were collected, and the expression of MFN2 and its relationship with survival were analyzed. The lentiviruses with MFN2 overexpression were constructed and infected with MG63 and U2OS cells. To investigate the effect of up-regulation of MFN2 expression on proliferation and apoptosis of osteosarcoma cells. The purified FLAG-MFN2 protein was analyzed by mass spectrometry and IP to verify the interaction between MFN2 and osteosarcoma. The correlation and mechanism between MFN2 and osteosarcoma were studied. Results the expression of MFN2 in osteosarcoma was lower than that in the adjacent tumor, and the level of MFN2 was positively correlated with the survival rate of osteosarcoma. The inhibitory effect of MFN2 on osteosarcoma was confirmed to be the first time to find that the interaction of MFN2 and PLK1 could down-regulate the expression of MFN2 and PLK1 in MFN2PPR-cas9. Conclusion: MF-N2 is a new tumor suppressor gene of osteosarcoma, which is related to the negative regulation of PLK1. Targeted MFN2/PLK1 axis is expected to be a new approach to accurate medicine for osteosarcoma.
【学位授予单位】：三峡大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R738.1

【相似文献】