MiR-29介导NF-κB信号转导通路对腺性膀胱炎的调控机制

Cystitis glandularis (CG) is considered to be a potential pre-cancerous lesion of bladder cancer which is concerned with chronic inflammation primarily. But the molecular mechanism of CG inducted by inflammation has not been reported to this day. Our research team has found two signal pathways- - MAPK/ERK1/2 and JAK/STAT were involved in the CG process of rat firstly. On the base of early work, we plan to focus on the pathogenesis of inflammation induced CG, and to study further the key point of signal pathway from the animal model, cell and molecular levels. We intend to use RNA interference and ultrasonic irradiation micro-bubbles SonoVue mediated gene transfection technology to reveal the roles of NF-κB signal pathway and NF-κB dependent miR-29a/b/c during the regulatory of CG lesions. Study of these problems will help us understand the relationships of miR-29 upstream control genes and downstream target genes with the important inflammation-cancer coupling NF-κB signal path in the process of the inflammation induced CG. In addition, studies of the molecular mechanism of CG induced by inflammation thoroughly would provide more theory base and thinking including prevention, diagnosis and treatment of inflammation carcinogenicity transformation.

腺性膀胱炎（CG）被认为是膀胱癌潜在的癌前病变，多与慢性炎症有关，但是炎症诱导的分子机制，迄今国内外尚不清楚。本课题组首次发现了MAPK/ERK1/2及JAK/STAT两条信号通路参与了CG的发生。我们拟在前期工作的基础上，围绕"炎症诱导CG的发病机制"，深入信号通路的中心环节，利用RNA干扰以及超声辐照微泡SonoVue介导基因转染技术，从动物模型、细胞水平到分子水平等多方位探讨NF-κB信号通路在CG病变中的作用，鉴定参与调控CG病变NF-κB依赖的miR-29a/b/c，从而揭示炎症诱导CG过程中miR-29的上游调控基因和下游靶基因与重要炎症-癌症偶联信号通路NF-κB之间的相互联系，为炎症致癌性转化的预防、诊断及治疗提供更多的依据与思路。

本课题组首次发现了MAPK/ERK1/2及JAK/STAT两条信号通路参与了CG的发生。我们在前期工作的基础上，围绕“炎症诱导CG的发病机制”，深入信号通路的中心环节，利用RNA干扰技术，从动物模型、细胞水平到分子水平等多方位探讨NF-κB信号通路在CG病变中的作用，鉴定参与调控CG病变NF-κB依赖的miR-29a/b/c，从而揭示炎症诱导CG过程中miR-29的上游调控基因和下游靶基因与重要炎症-癌症偶联信号通路NF-κB之间的相互联系。此外，我们筛选出膀胱癌新基因Mex3a，通过生存分析及功能分析证实Mex3a基因促进膀胱癌细胞（5637）的增殖，抑制膀胱癌细胞的凋亡。为炎症致癌性转化的预防、诊断及治疗提供更多的依据与思路。