circESRP1作为ceRNA调控TGF-β介导的信号通路参与小细胞肺癌化疗耐药的机制

化疗耐药是导致小细胞肺癌（SCLC）患者预后差的重要因素。我们前期发现circESRP1在SCLC耐药细胞H69AR中显著下调，沉默敏感细胞H69中circESRP1表达，细胞对顺铂等化疗药物产生抗药性，同时还发现circESRP1与miR-93-5p间存在作用关系，影响TGF-β通路中SMAD7和P21/CDKN1A表达。据此我们提出circESRP1可能通过竞争性结合miR-93-5p，调控TGF-β介导下的信号通路，参与SCLC耐药调节的假说。本课题拟利用耐药细胞模型（H69AR和H446DDP）和SCLC患者组织标本，进一步明确circESRP1在SCLC化疗耐药中的作用；运用Western blot、荧光素酶、RIP等技术阐明circESRP1通过ceRNA调控TGF-β介导的信号通路，参与SCLC耐药的机制。通过本项目研究，为寻找SCLC耐药的分子标记物和治疗靶点提供科学依据。

Chemoresistance is the major cause of poor prognosis in small cell lung cancer (SCLC) patients. Our preliminary study present circESRP1 was down-regulated in multi-drug resistance H69AR cells by circlRNA microarray. circESRP1 knockdown significantly promotes H69 cells chemoresistance to anti-cancer drugs including DDP etc. We also fund circESRP1 may interact with miR-93-5p and upregulate SMAD7 and P21/CDKN1A expression which two of important members of TGF-β mediated signaling pathway. Taken together, we suggest that circESRP1 may be involved in chemoresistance of SCLC by acting as a competitive endogenous RNA of miR-93-5p to modulate TGF-β mediated signaling pathway. In this project, we intend to use the model of small cell lung cancer resistant cells (H69AR and H446DDP) and SCLC tissues to further confirm the role of circESRP1 in SCLC chemoresistance. We also elucidate the mechanism of circESRP1 regulate SCLC chemoresistance by TGF-β mediated signaling pathway using Western blot, luciferase reporter gene and RNA immunoprecipitation (RIP) assay. Through this research project, we will provide the evidence for finding biological marker and the targeting gene of small cell lung cancer chemoresistance.