核糖核蛋白NOP10通过蛋白翻译过程调控非小细胞肺癌发生发展的机制研究

非小细胞肺癌（NSCLC）是世界范围内癌症死亡的主要原因之一，阐明其发生发展机制将有助于临床寻找新的靶标及治疗方案。NSCLC发生发展与细胞蛋白合成过度活跃密切相关，核糖核蛋白复合物参与的核糖体RNA（rRNA）合成是细胞蛋白合成的核心调控步骤。前期发现NOP10在NSCLC组织表达上调，可导致患者预后不良；NOP10高表达与细胞蛋白翻译激活存在相关性，敲减NOP10可抑制核仁小RNA（snoRNA）表达，减少细胞内新生蛋白合成。推测NOP10通过snoRNA介导的细胞蛋白翻译过程是NSCLC发生发展的关键调控环节。本项目拟通过CRISPR/Cas9高通量筛选及假尿苷测序研究NOP10调控rRNA生物合成过程，并从蛋白翻译层面揭示NOP10调节细胞蛋白合成、促进NSCLC发生发展的机制。本课题从独特的角度研究肿瘤细胞蛋白翻译，加深对NSCLC发生发展机制的认识，为其治疗提供重要的科学依据。

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. It is urgent to understand the specific mechanism of NSCLC to find new target and strategy for clinical therapy. The development of NSCLC is highly correlated with hyperactivity of cellular protein synthesis. The ribosomal RNA (rRNA) biogenesis involved in small nucleolar ribonucleoproteins (snoRNPs) is the key point to regulate protein synthesis of cells. Our previous investigation identified that NOP10 is upregulated in NSCLC tissues and correlated with poor patient prognosis. And protein translation of tumor cells is closely correlated with NOP10 expression. NOP10 knockdown significantly reduced expression of small nucleoar RNA (snoRNA) and inhibited new protein synthesis in NSCLC cells. We speculated that the protein translation procedure, regulated by NOP10 mediated snoRNA, is the key point for NSCLC development. In this study, we will deeply study the mechanism of rRNA synthesis regulated through CRISPR/Cas9 high-throughput screening and rRNA pseudouridylation analysis. From the perspective of protein translation, we will further investigate the mechanism of how NOP10 regulates protein synthesis and promotes NSCLC development. This project is to understand the mechanism of NSCLC pathogenesis and development from the unique perspective of protein translation, so as to provide new scientific basis for the treatment of NSCLC.