胰腺癌是一种预后极差的消化道恶性肿瘤，亟需阐明其发生发展机制，寻找关键调控靶点以获得防治突破。ZHX1在肿瘤的发生发展中扮演着不同的角色，但ZHX1在胰腺癌中的作用及机制尚不清楚。我们前期预实验发现，ZHX1在胰腺癌组织中低表达，抑制胰腺癌细胞增殖和侵袭能力；miR-186-5p及其靶基因ZHX1同时受到转录因子YY1的调控。 为此，我们提出科学假说：YY1在转录水平抑制ZHX1的表达，同时转录激活miR-186；成熟的miR-186-5p在转录后水平抑制ZHX1的表达，即通过形成前馈环模式加强了对ZHX1的下调作用，从而减弱了ZHX1在胰腺癌中的抑癌作用。我们通过临床标本及数据分析、细胞分子机制研究和动物实验验证三个层次探索YY1/miR-186-5p/ZHX1所形成的前馈环在胰腺癌细胞增殖和侵袭中的作用和分子机制，同时为胰腺癌的临床诊治策略提供新的思路。

Pancreatic cancer is a type of gastrointestinal malignancy with poor prognosis. It is urgent to clarify the mechanisms and find the key targets to achieve breakthroughs in prevention and treatment. ZHX1 plays different roles in the development and progression of tumor, but the role and mechanism of ZHX1 in pancreatic cancer are still unclear. Our preliminary experiments showed that ZHX1 was down regulated in pancreatic cancer tissue, which inhibited the proliferation and invasion of pancreatic cancer cells. MiR-186-5p and its target gene ZHX1 are simultaneously regulated by the transcription factor YY1. Based upon the previous reports, we propose a scientific hypothesis that YY1 inhibits the expression of ZHX1 at the transcriptional level, and simultaneously activates mir-186. Mature mir-186-5p inhibits the expression of ZHX1 at the post-transcriptional level, that is, it strengthens the down-regulation of ZHX1 by forming a feed-forward loop mode, thereby weakening the tumor suppressive effect of ZHX1 in pancreatic cancer. We explored the role and molecular mechanism of YY1/miR-186-5p/ZHX1 feed-forward loop in the proliferation and invasion of pancreatic cancer cells through three levels，including the analysis of clinical specimens and data, the study of cellular and molecular mechanisms, and the verification of animal experiments. At the same time, it provides new ideas for the clinical diagnosis and treatment of pancreatic cancer.