【作者】 易伟峰；

【导师】 胡维新；

【作者基本信息】 中南大学 ， 软件工程， 2013， 硕士

【摘要】 摘要：多发性骨髓瘤(multiple myeloma, MM)是一种常见于中老年人的血液系统恶性肿瘤,由浆细胞克隆性增生所致。MM发病机制相当复杂,由于染色体易位的发生,使MM细胞呈现出遗传多样性。MM细胞具有非常复杂的核型,表现为染色体数量的异常及染色体结构的异常。Clorf35基因是一个与MM高度相关的恶性基因,前期研究结果显示Clorf35能促使细胞转化,促进细胞生长、增殖,并能使裸鼠成瘤。但是,Clorf35基因在MM致病过程中的功能目前尚不明确。本文在前期研究的基础上,采用RT-PCR方法,比较了MM患者与正常健康成人中Clorf35基因的表达水平。同时,采用生物信息学方法,从DNA、RNA及蛋白质结构三方面着手,预测Clorf35基因的功能结构域及其相互作用蛋白质,推测Clorf35可能参与的信号转导途径,从而明确Clorf35的功能。这将为进一步采取合适的实验方法去验证Clorf35基因在MM发生、发展中的作用提供依据。结果表明,在29例MM患者中,Clorf35基因表达明显上调(21/29)。生物信息学分析结果显示,Clorf35蛋白定位于细胞核中,具有多个蛋白激酶的磷酸化位点和N-豆蔻酰化位点,提示它可能作为一种核内信号分子,参与细胞信号传递并在调节决定细胞命运的基因表达过程中发挥作用。Clorf35的相互作用蛋白包括THAP1等调控细胞周期的蛋白,提示Clorf35可能通过参与细胞内多条信号转导途径而调控细胞生长、增殖。更多还原

【Abstract】 Abstract:Multiple myeloma (MM) is a hematological malignancy characterized by the uncontrolled proliferation of monoclonal plasma cells. MM is common in old people. Because of the chromosome translocation, MM cells showed different number and structure abnormalities of some chromosomes.Clorf35gene is a novel multiple myeloma tumor-associated gene. The studies showed that Clorf35can lead to cell transformation and promote cell proliferation. In addition, Clorf35cause tumorigenic ability in nude mice experiments. But, how does Clorf35function in MM pathogenesis is still unknown.In this research, by using RT-PCR, we compared the expression levels of Clorf35gene in MM samples and health groups. At the same time, by analyzing the DNA, RNA and protein structures of Clorf35, we predicted the interaction proteins and functional domains of Clorf35, and possible signal transduction pathways taking part in by Clorf35. These would provide evidences for further research on the important function of Clorf35.The results showed that Clorf35is distinctly overexpressed in MM samples (21/29). Bioinformatics analysis showed the encoded products of Clorf35are located at cell nuclus. Clorf35is a kinase phosphorylation protein, there is a glycine-rich domain that is the most highly conserved region of a family of proteins that in vertebrates are associated with tumors in MM. The region may contain phosphorylation sites for several protein kinases, as well as N-myristoylation sites and nuclear localization signals, so it might act as a signal molecule in the nucleus. The interaction protein of Clorf35protein includes THAP1, which is associated with regulating cell cycle progress. This suggests Clorf35regulate cell growth and proliferation by many pathways.更多还原