CENP-N/USP37通过介导有氧糖酵解增强酸性微环境促进鼻咽癌侵袭转移

最近有研究发现CENP-N对肿瘤的发生、发展起了明显的促进作用。但其与肿瘤转移的关系尚未见报道。我们前期研究发现：鼻咽癌组织中CENP-N表达高的患者鼻咽部肿瘤葡萄糖摄取水平增加；发生区域淋巴结转移的风险升高。抑制鼻咽癌5-8F细胞CENP-N表达后：侵袭转移、有氧糖酵解、葡萄糖摄取及乳酸堆积受到抑制；基因转录组测序发现癌细胞中USP37表达下调；其USP37全长启动子活性降低、mRNA和蛋白水平明显下调。据此，我们提出设想：CENP-N通过USP37介导有氧糖酵解增强酸性微环境促进鼻咽癌侵袭转移。本项目拟研究CENP-N表达多大程度影响鼻咽癌细胞的侵袭、转移？CENP-N是否通过USP37调控有氧糖酵解改变肿瘤酸性微环境促进鼻咽癌细胞的转移？CENP-N如何影响USP37的表达？这些问题的研究将明确CENP-N对鼻咽癌侵袭转移的作用及分子机制，为伴有转移的鼻咽癌治疗提供新视野与新策略。

Recent studies have revealed the important role of CENP-N in promoting tumorigenesis and progression. However, the relationship between CENP-N and tumor metastasis has not been reported yet. Our previous study found that nasopharyngeal carcinoma (NPC) with highly CENP-N expression showed increased ability of glucose uptake and regional lymphatic metastasis; inhibition of CENP-N levels in 5-8F cells could exactly suppress cell invasion, metastasis, aerobic glycolysis, glucose uptake and lactic acid accumulation. When CENP-N expression was inhibited, RNA sequencing analysis found that the expression of USP37 was down-regulated in cancer cells, additionally, the full-length promoter of USP37 showed low-activity, with decreased USP37 mRNA and protein levels. Therefore, we propose the hypothesis that CENP-N enhanced acidic microenvironment through USP37-mediated aerobic glycolysis to promote the invasion and metastasis of NPC. In this study, we examined the following questions: To what extent does CENP-N affect the invasion and metastasis of NPC cells？Whether CENP-N enhances acidic microenvironment through USP37-mediated aerobic glycolysis to promote the invasion and metastasis of NPC? How does CENP-N affect the expression of USP37? This study will clarify the importance of CENP-N in the invasion and metastasis of NPC, as well as its underlying molecular mechanisms, aiming to provide a new vision and strategy for the treatment of NPC with metastasis.