miR-7-5p调控mTORC1-AMBRA1-c-Myc信号轴影响DLBCL自噬和凋亡“交叉对话”以及益气除痰方的干预机制

Diffuse large B cell lymphoma (DLBCL) is the most common non Hodgkin lymphoma with a high degree of invasiveness. Previous studies have proved that the Yiqichutan recipe can reduce the toxicity and increase the efficiency of chemotherapy in DLBCL, which is related to the induction of apoptosis by regulating the PI3K and c-Myc pathways, but the rate of apoptosis is not high. Previous studies found that Yiqichutan recipe can induce autophagy and up-regulate the autophagy gene AMBRA1. The gene has been reported to play a dual role in regulating autophagy and apoptosis, and is regulated by miR-7-5p. Therefore, we put forward the scientific question: Yiqichutan recipe can interfere the autophagy and apoptosis of DLBCL by intervening miR-7-5p and regulating mTORC1- AMBRA1-c-Myc axis. This project will observe the dynamic changes of autophagy and apoptosis in DLBCL from the levels of in vivo and in vitro, and clarify the specific mechanism of regulating miR-7-5p/mTORC1-AMBRA1-c-Myc signaling pathway from the molecular level under the action of Yiqichutan recipe. This topic will reveal the mechanism of regulating the network of autophagy and apoptosis by Yiqichutan recipe, and explore the method of increasing the efficiency of the recipe, which has important theoretical and practical value.

弥漫大B细胞淋巴瘤（DLBCL）是最常见的非霍奇金淋巴瘤，具有高度侵袭性。前期研究证明益气除痰方联合化疗治疗DLBCL可以减毒增效，与其通过调控PI3K及c-Myc通路诱导DLBCL凋亡有关，但观察到的凋亡率并不高。前期研究初步发现益气除痰方可以诱导自噬，并上调自噬基因AMBRA1，文献报道该基因具有调控自噬与凋亡的双重作用并受miR-7-5p调控。由此我们提出科学假说：益气除痰方通过干预miR-7-5p，调控mTORC1-AMBRA1-c-Myc轴影响DLBCL细胞自噬和凋亡“交叉对话”。本项目将从体内（动物）、体外（细胞）水平上观察益气除痰方作用下DLBCL自噬和凋亡的动态变化，并从分子水平明确益气除痰方调控miR-7-5p/mTORC1-AMBRA1-c-Myc信号通路的具体机制。本课题将揭示益气除痰方调控自噬和凋亡网络的机制，并探索益气除痰方的增效方法，具有重要理论和应用价值。

弥漫大B细胞淋巴瘤（DLBCL）是最常见的非霍奇金淋巴瘤，具有高度侵袭性。前期研究证明益气除痰方联合化疗治疗DLBCL可以减毒增效，与其通过调控PI3K及c-Myc通路诱导DLBCL凋亡有关，但观察到的凋亡率并不高。前期研究初步发现益气除痰方可以诱导自噬，并上调自噬基因AMBRA1，文献报道该基因具有调控自噬与凋亡的双重作用并受miR-7-5p调控。由此我们提出科学假说：益气除痰方通过干预miR-7-5p，调控mTORC1-AMBRA1-c-Myc轴影响DLBCL细胞自噬和凋亡“交叉对话”。本项目将从体内（动物）、体外（细胞）水平上观察益气除痰方作用下DLBCL自噬和凋亡的动态变化，并从分子水平明确益气除痰方调控miR-7-5p/mTORC1-AMBRA1-cMyc信号通路的具体机制。本课题将揭示益气除痰方调控自噬和凋亡网络的机制，并探索益气除痰方的增效方法，具有重要理论和应用价值。