lncRNA SHILA通过ENO1/AMPK/mTOR信号通路增强肝癌RFA后残癌细胞自噬的机制研究

细胞自噬在肿瘤发生发展过程中起重要作用。课题组研究发现不全射频消融（IRFA）后残癌细胞自噬增强，ATP-AMPK-mTOR信号通路激活，但其激活的具体机制尚不清楚。研究报道lncRNA调控肝癌细胞自噬，但lncRNA调控IRFA后残癌细胞自噬目前尚未见研究报道。课题组研究发现残癌细胞稳定高表达lncRNA SHILA，与ENO1结合且负调控ENO1表达。新近研究提示ENO1能够调控AMPK-mTOR信号通路。因此我们提出假设：lncRNA SHILA负调控ENO1表达，从而激活AMPK-mTOR信号通路，增强IRFA后残癌细胞自噬，且该lncRNA在此过程是必需的。本项目拟以残癌为研究对象，利用RNA pulldown、基因调控等技术，深入探索lncRNA SHILA增强残癌细胞自噬的具体分子机制，为提高肝癌RFA疗效提供理论依据。

Autophagy plays an important role in tumor development. The research group found that autophagy was enhanced and the ATP-AMPK-mTOR signaling pathway was activated after incomplete radiofrequency ablation (IRFA), but the specific mechanism of its activation is still unclear.Studies have reported that lncRNA regulates autophagy of liver cancer cells, but there has been no report on autophagy of residual cancer cells after lncRNA regulates IRFA.The research group found that the residual cancer cells had stable and high expression of lncRNA SHILA, which was bound to ENO1 and negatively regulated the expression of ENO1.Recent studies suggest that ENO1 can regulate AMPK-mTOR signaling pathway.Therefore, we hypothesized that lncRNA SHILA negatively regulated ENO1 expression to activate AMPK-mTOR signaling pathway and enhance autophagy of residual cancer cells after IRFA, and that lncRNA was necessary in this process.This project intends to take residual cancer as the research object, and use RNA pulldown, gene regulation and other technologies to deeply explore the specific molecular mechanism of lncRNA SHILA enhancing autophagy of residual cancer cells, so as to provide theoretical basis for improving the efficacy of RFA in hepatocellular carcinoma.