核糖体蛋白L34通过MYC/RPL34/EIF3A信号轴调控人骨肉瘤细胞增殖的机制研究

Osteosarcoma is the most common primary malignant bone tumor. Recent studies have found that ribosomal protein L34 (RPL34) play an important role in the proliferation of some malignant tumors，including osteosarcoma. But the molecular mechanism that RPL34 affects the proliferation of malignant tumor cells still remains unknown. Our previous study has found that the expression of RPL34 in osteosarcoma tissues is significantly higher than that in both adjacent non-cancerous tissues and normal bone tissues, and that the signaling pathway of MYC/RPL34/EIF3A might affect the proliferation of osteosarcoma cells. Based on the previous study, we plan to regulate RPL34 expression in human osteosarcoma cell lines, and then conduct cytology and animal experiments in order to find the effects of RPL34 on the proliferation of human osteosarcoma cells. Luciferase assay、DNA-protein and protein-protein interaction studies will be performed, combined with the proliferation test of osteosarcoma cells with knockdown or over-expression of MYC、RPL34 and EIF3A, to confirm that MYC promotes osteosarcoma cell proliferation through enhancing RPL34 transcription and the interaction of RPL34 with EIF3A. Our research has a great significance in clarifying the molecular mechanism through which abnormal expression of RPL34 affects the proliferation of human osteosarcoma cells. It will give a new insight into the targeting therapy of osteosarcoma.

骨肉瘤是最常见的原发恶性骨肿瘤。近年来研究发现，核糖体蛋白L34（RPL34）在包括骨肉瘤在内的恶性肿瘤的增殖中扮演了重要角色，但其分子机制仍不清楚。我们前期研究发现，RPL34在人骨肉瘤组织中的表达高于癌旁组织和正常骨组织，并且“MYC/RPL34/EIF3A”信号轴可能参与了人骨肉瘤细胞的增殖调控。本课题拟对多株人骨肉瘤细胞的RPL34表达进行调控，采用细胞学实验和动物实验进一步明确RPL34对人骨肉瘤细胞增殖的影响；通过萤光素酶报告基因检测、蛋白-DNA及蛋白-蛋白的体内外互作实验，和对骨肉瘤细胞中MYC、RPL34及EIF3A进行干扰或过表达调控后的增殖检测，来阐明MYC通过提高RPL34基因的转录表达和RPL34与下游EIF3A的相互作用，而促进了人骨肉瘤细胞的增殖。本研究对于阐明RPL34影响人骨肉瘤细胞增殖的机制具有重要意义，为骨肉瘤的靶向治疗提供新的思路。

骨肉瘤是最常见的原发恶性骨肿瘤。核糖体蛋白L34（RPL34）在骨肉瘤在内的恶性肿瘤的增殖中扮演了重要角色，RPL34在人骨肉瘤组织中的表达高于癌旁组织和正常骨组织，本课题对多株人骨肉瘤细胞的RPL34表达进行调控，采用细胞学实验和动物实验进一步明确RPL34对人骨肉瘤细胞增殖的影响；通过萤光素酶报告基因检测、蛋白-DNA及蛋白-蛋白的体内外互作实验，和对骨肉瘤细胞中MYC、RPL34及EIF3A进行干扰或过表达调控后的增殖检测，来阐明MYC通过提高RPL34基因的转录表达和RPL34与下游EIF3A的相互作用，而促进了人骨肉瘤细胞的增殖，发现“MYC/RPL34/EIF3A”信号轴参与了人骨肉瘤细胞的增殖调控。本研究对于阐明RPL34影响人骨肉瘤细胞增殖的机制具有重要意义，为骨肉瘤的靶向治疗提供新的思路。