circHIPK2竞争性结合miR-200c调控TGF-β/Smads信号通路诱导EMT促大肠癌转移的机制及补肾解毒散结方的干预作用

circHIPK2是一种非编码环状RNA，作为癌基因参与肿瘤发生发展。miR-200c是TGF-β/Smads通路的抑制因子，可被circHIPK2吸附，形成circHIPK2/miR-200c开关，调控EMT和转移。我们发现circHIPK2在大肠癌中过表达，与转移密切相关，但机制尚不清楚。肾虚与癌毒互结，导致大肠癌“肾精亏虚、癌毒传舍”发生转移。基于补肾解毒散结方调节HIPK2和TGF-β/Smads通路抑制转移的前期基础，提出科学假说：补肾解毒散结方通过circHIPK2/miR-200c开关，调控TGF-β/Smads通路抑制大肠癌EMT和转移。.本课题以人大肠癌组织、细胞和裸鼠模型为实验对象，采用基因编辑、蛋白芯片、动物活体成像等技术，从TGF-β/Smads信号转导角度，研究补肾解毒散结方调控circHIPK2逆转EMT抑制大肠癌转移的机制，为中医药防治大肠癌转移提供科学依据。

CircHIPK2 is a non-coding circRNA that is involved in tumorigenesis and development as an oncogene. miR-200c is an inhibitor of the TGF-β/Smads pathway and can be absorbed by circHIPK2 to form the circHIPK2/miR-200c switch, which regulates EMT and metastasis. Our previous research found that circHIPK2 was overexpressed in colorectal cancer, which was significantly correlated with metastasis, but the mechanism is unclear. The combination of kidney essence deficiency and cancer toxicity induced colorectal cancer metastasis because of "kidney essence deficiency and cancer toxicity transmission". Based on the preliminary basis that Bushen Jiedu Sanjie recipe could regulate HIPK2 and TGF-β/Smads pathway to inhibit the metastasis, we proposed the following scientific hypothesis: The Bushen Jiedu Sanjie recipe could inhibit colorectal cancer metastasis by down-regulating the TGF-β/Smads signaling pathway through the circHIPK2/miR-200c switch..In this study, human colorectal cancer tissue, cells and nude mouse models were used to study. Gene editing, protein microarray, animal in vivo imaging and other technologies were used to study the mechanism of regulating circHIPK2 by Bushen Jiedu Sanjie recipe to reverse EMT inhibition of colorectal cancer metastasis from the perspective of TGF-β/Smads signal transduction, providing a scientific basis for Traditional Chinese Medicine prevention and treatment of colorectal cancer metastasis.