胃癌腹膜转移是癌细胞与腹膜微环境相互作用的结果，其中腹膜间皮细胞发挥重要作用。前期工作证实，间皮细胞自噬促进胃癌细胞粘附、侵袭进而促进腹膜转移。其中间皮细胞自噬性分泌HMGB1是促进腹膜转移的关键因子。进一步分析发现，胃癌细胞外泌体可诱导间皮细胞自噬，外泌体中长非编码RNA lnc-BER可结合自噬相关基因BECN1的mRNA，并正向调控BECN1表达。综上我们推测，胃癌细胞外泌体lnc-BER通过靶向结合间皮细胞BECN1 mRNA稳定其表达，激活间皮细胞自噬并分泌HMGB1，最终诱导腹膜转移的发生。本项目拟通过分子生物学实验方法，重点研究胃癌外泌体lnc-BER对BECN1的调控作用以及间皮细胞自噬性分泌HMGB1对腹膜转移的影响这一核心科学问题。研究结果将为胃癌腹膜转移提供新的思路与潜在治疗靶点。

Gastric cancer peritoneal dissemination is the consequence of the interaction between cancer cells and peritoneal microenvironment, in which peritoneal mesothelial cells play an important role. Our previous studies revealed that autophagy of peritoneal mesothelial cells promoted gastric cancer cells adhesion, invasion and peritoneal dissemination. Autophagic secretion of HMGB1 by mesothelial cells was the key factor to induce peritoneal dissemination. Further analysis showed that exosomes derived from gastric cancer enhanced autophagy of mesothelial cells. A long noncoding RNA lnc-BER from gastric cancer exosomes could bind to the autophagy related gene BECN1 mRNA and up-regulate the expression of BECN1. In conclusion, we speculated that exosomal lnc-BER released from gastric cancer could stabilize BECN1 expression by binding BECN1 mRNA. Then mesothelial cells autophagy was activated and secreted HMGB1 to promote peritoneal dissemination. In this study, we will focus on the regulation of BECN1 by lnc-BER and the effect of mesothelial cells autophagic secretion HMGB1 on peritoneal dissemination. Our results would provide novel insights and potential therapeutic targets for gastric cancer peritoneal dissemination.