逆转小细胞肺癌（SCLC）耐药是临床亟需解决的重要问题。有研究初步提示转录抑制因子（CDYL）有可能通过募集甲基转移酶EZH2调控H3K27三甲基化（H3K27me3），但并未见其参与调节肿瘤耐药的报道。我们前期首次发现：CDYL在SCLC耐药细胞株中高表达，下调其表达可降低肿瘤细胞耐药性；同时H3K27me3减少，药物敏感基因hMLH1表达增高；过表达hMLH1可降低耐药。据此，我们认为CDYL有可能通过EZH2调控hMLH1启动子区H3K27me3，进而促进SCLC耐药。为验证假设，本项目拟进一步在SCLC临床标本中证实CDYL与耐药的相关性；然后，利用体内外实验明确CDYL可促进SCLC耐药；最后，通过荧光素酶/ChIP等实验，在SCLC中重点探讨CDYL通过调控hMLH1启动子H3K27me3抑制其转录的机制。本项目有望为SCLC耐药逆转机制研究提供新思路。

Reversing the chemoresistance of SCLC（Small Cell Lung Cancer, SCLC）is an important problem to be solved. Some studies preliminarily showed that CDYL can regulate the expression of H3K27 trimethylation catalyzed by EZH2（enhancer of zeste homologue 2，EZH2）. However, the relationship between CDYL and chemoresistance is still unknown. Our previous study showed that the expression of transcriptional repressor CDYL（Chromodomain Y-like, CDYL）in the SCLC drug resistance cell H69/AR was higher than that in the sensitive cell H69. Furthermore, down-regulation of CDYL in the H69/AR cell reversed the chemoresistance, and inhibited the expression of H3K27 trimethylation, but promoted the expression of drug sensitivity gene hMLH1. Besides, over-expression of hMLH1 reduced the chemoresistance of SCLC. Thus, we propose a hypothesis that CDYL promotes the chemoresistance of SCLC by regulating the H3K27 trimethylation in the promoter region of hMLH1. To test our hypothesis, we formulate the following studies. Firstly, the relationship between CDYL and chemoresistance in the clinical samples is to be analyzed. Secondly, whether CDYL promotes the chemoresistance is to be verified in the SCLC chemoresistance cells and animal experiments. Then, the experiments such as luciferase assay and Chip experiment are performed to investigate whether CDYL promotes the chemoresistance of SCLC by regulating the H3K27 trimethylation in the promoter region of hMLH1. We may provide a new method to reverse the chemoresistance of SCLC by targeting the expression of CDYL.