C1orf35在多发性骨髓瘤中参与c-MYC转录后调控的机制研究

多发性骨髓瘤（Multiple Myeloma，MM）的发生发展中，1号染色体的结构异常是最常见的继发性遗传事件。C1orf35是我们课题组首次克隆并鉴定的与MM相关的全新候选癌基因。通过RNA免疫共沉淀,我们发现C1orf35能与c-MYC mRNA相互作用,且C1orf35能增加c-MYC mRNA稳定性。在本项目中，我们将确定C1orf35作为候选的RNA结合蛋白与c-MYC mRNA结合的结合域及c-MYC mRNA结合C1orf35的结合位点，并以此来研究C1orf35对c-MYC转录后调控，及对MM细胞克隆演变的影响。我们将构建ARH-77-CRISPERi-C1orf35细胞系，通过MM动物模型研究C1orf35作为一个潜在治疗靶点的可行性；通过检测病人骨髓及外周血中C1orf35与c-MYC表达水平，确定C1orf35可否作为MM诊断分子标记物。

Aberrations in chromosome 1 are considered the most common secondary cytogenic abnormalities in the development of Multiple Myeloma (MM). C1orf35 (Chromosome 1 open reading frame 35) is a novel candidate oncogene cloned and identified in our laboratory that is associated with MM. By conducting RNA immunoprecipitation, we found that C1orf35 is able to interact with c-MYC mRNA. We also found that C1orf35 is able increase c-MYC mRNA stability. In the current study, we will find the binding domain of C1orf35 and binding site of c-MYC mRNA in their interaction, and we will further explore the role of C1orf35 as a candidate RNA binding protein in the post-transcription regulation of c-MYC and how it affects the clonal evolution of MM cells. Moreover, we will establish ARH-77-CRISPERi-C1orf35 cell line, and explore whether C1orf35 can be considered as a potential therapeutic target. Finally, we will explore whether C1orf35 can be used as a diagnostic marker in MM by detecting C1orf35 and c-MYC expression in patients' bone marrow and peripheral blood samples.