LINC02528调控EEF1A2促进鼻咽癌转移的机制研究

远处转移是当前鼻咽癌临床治疗失败的主要原因，lncRNA在肿瘤转移中起重要调控作用。前期研究发现：①LINC02528在鼻咽癌组织和细胞系中高表达，体外敲减LINC02528的表达能够抑制鼻咽癌细胞的转移和增殖能力；②RNA pull-down结合质谱分析发现LINC02528可与真核翻译延伸因子EEF1A2结合，敲减LINC02528的表达能够抑制EEF1A2的GTP酶活性；③小样本生存分析结果显示LINC02528高表达患者的预后较差。根据前期研究结果，我们提出以下科学假说：LINC02528通过与EEF1A2结合并提高其GTP酶活性，增强下游靶基因的翻译从而促进鼻咽癌转移。基于此，本项目拟聚焦LINC02528的体内外功能，阐明LINC02528-EEF1A2促进鼻咽癌转移的分子机制，明确其临床预测价值，并以期为鼻咽癌高转移风险患者提供有效的预后指标和潜在靶点。

Distant metastasis is the main cause of failure in clinical treatment of nasopharyngeal carcinoma. lncRNAs play an important role in the regulation of tumor metastasis. Previous studies have shown that: ①LINC02528 is highly expressed in NPC tissues and cell lines. Knockdown of LINC02528 expression in vitro could inhibit the metastasis and proliferation of NPC cells. ②RNA pull-down binding mass spectrometry showed that LINC02528 could bind to eukaryotic transcription elongation factor EEF1A2. Knockdown of LINC02528 could inhibit the GTPase activity of EEF1A2. ③Small scale clinical sample analysis showed that patients with high expression of LINC02528 had poor prognosis. Based on the results of previous studies, we proposed the hypothesis that LINC02528 promotes nasopharyngeal carcinoma metastasis by binding to EEF1A2 and enhancing its GTPase activity, thus enhancing the translation of downstream target genes. This project aims to focus on the in vivo and in vitro functions of LINC02528, clarify the molecular mechanism of LINC02528-EEF1A2 in promoting nasopharyngeal carcinoma metastasis and validate its clinical predictive value, which may provide effective prognostic indicators and potential targets for patients with high risk of nasopharyngeal carcinoma metastasis.