奥沙利铂耐药是影响结直肠癌患者预后的重要因素，深入阐明耐药发生的分子机制、发现可用于耐药预测的分子标志物至关重要。本项目前期利用奥沙利铂耐药细胞进行ChIP-seq 及RNA-seq研究，发现超级增强子相关的lncRNA Z97634.1（SE-lncRNA Z97634.1）在耐药细胞中表达显著升高且与奥沙利铂耐药密切相关；进一步分析发现Z97634.1主要位于细胞核且上调MRP2 mRNA的表达。本研究拟在前期研究基础上从体外、体内及临床样本等层面：明确SE-lncRNA Z97634.1促进奥沙利铂耐药的功能；阐明SE-lncRNA Z97634.1在转录水平上调MRP2表达的分子机制；利用临床大样本资源，探究血清SE-lncRNA Z97634.1在结直肠癌患者奥沙利铂耐药中的预测价值。本研究将有助于揭示奥沙利铂耐药的分子调控机制，发现新型耐药预测标志物，为克服耐药提供思路。

Oxaliplatin resistance is an important factor affecting the prognosis of patients with colorectal cancer. It is important to clarify the molecular mechanism of drug resistance and find molecular markers that can be used to predict drug resistance. Early in the project, ChIP-seq and RNA-seq studies were performed using oxaliplatin-resistant cells. It was found that super enhancer-associated lncRNA Z97634.1 (SE-lncRNA Z97634.1) was significantly increased in drug-resistant cells and closely related to oxaliplatin resistance; further analysis found that Z97634.1 is located in the nucleus and up-regulatee the expression of MRP2 mRNA. Based on previous research, this study intends to determine at in vitro, in vivo and clinical sample aspects: the function of SE-lncRNA Z97634.1 in oxaliplatin resistance of colorectal cancer; clarify the molecule regulatory mechanism by which SE-lncRNA Z97634.1 upregulates MRP2 expression at the transcription level; using clinical large sample resources to explore the predictive value of serum SE-lncRNA Z97634.1 in oxaliplatin-resistant colorectal cancer patients. This study not only helps reveal the molecular regulatory mechanism of oxaliplatin resistance, but also help discover new predictive markers for chemoresistance, providing ideas for overcoming resistance.