LncRNA-NR在肝癌干细胞中的生物学功能研究

Cancer stem cells (CSCs) lead to tumor recurrence, metastasis and drug resistance, making tumor a serious threat to the patient’s life quality. Self-renewal regulatory mechanism has become a novel idea to design strategy of specifically targeting CSCs. Nanog, a pluripotent stem cell factor, maintain cancer stem cell self-renewal and promote tumor metastasis. Long chain non-coding RNA (lncRNA) is also found to be widely participate in tumor genesis and development, but its role in regulating CSCs is unclear. Our preliminary microarray screening have found that compared with the original site, abnormally higher expression of lncRNA-NR was spotted in metastasis site. Moreover, it could upregulate Nanog expression in liver cancer cells. Based on the above results, this study use liver cancer as object: 1. Use molecular biological methods and western blot technique conducting loss of function experiment to investigate the role of LncRNA NR/Nanog signaling pathways in regulating self-renewal of liver cancer stem cells; 2. Test the tumor treatment effect of this pathway on cell level and using the nude mice; 3. Investigate the relationship between lnRNA-NR level and prognosis of liver cancer patients. Through this research, we could provide an effective reference for the clinical treatment of tumor.

肿瘤干细胞导致肿瘤复发、转移和耐药性，严重威胁患者的生存质量。自我更新的调控机制是设计靶向清除肿瘤干细胞策略的切入点。我们的前期研究发现，干细胞多能因子Nanog维持肿瘤干细胞自我更新、促进肿瘤转移。长链非编码RNA（lncRNA）广泛参与肿瘤的发生发展，但在肿瘤干细胞中的调控作用不明。我们利用lncRNA芯片筛选发现，与原发灶相比，肝癌转移灶中有大量异常表达的lncRNA，其中lncRNA-NR超高表达，并且能够上调Nanog在肝癌细胞中的表达。本研究在这个基础上以肝癌为对象：1、利用分子生物学、免疫印迹等技术在细胞水平通过功能缺失与获得研究LncRNA-NR/Nanog信号通路调节肝癌干细胞自我更新的作用机制；2、利用细胞和裸鼠研究以该通路为切入点的肿瘤治疗效果；3、lncRNA-NR表达水平与临床肝癌患者预后之间的关系。通过这一研究以期为临床治疗肿瘤提供有效的参考方案。