肺癌是我国目前发生率和死亡率最高的恶性肿瘤。前期研究发现舌癌耐药相关蛋白(TCRP1)在肺癌中表达畸高并因此导致肺癌细胞对顺铂耐受，故揭示TCRP1的表达调控机制是理解其在肺癌中发挥相应功能的关键。申请者发现肺癌细胞中p53及乙酰转移酶抑制剂均可下调TCRP1表达；p53、甲基胞嘧啶双加氧酶2 (TET2)及组蛋白去乙酰转移酶2 (Hdac2)间可能通过复合物的形式在TCRP1启动子区发挥调控作用。本课题拟分析肺癌中p53、TET2与TCRP1表达的相关性，明确p53/TET2/Hdac2复合物调控TCRP1表达的具体方式，并在体内水平和临床组织标本中验证该复合物对TCRP1的转录调控作用，阐明p53/TET2/Hdac2蛋白复合物调控肺癌TCRP1转录表达的机制，为进一步丰富肺癌发生及化疗耐受网络机制研究、开展以TCRP1及其调控分子为靶标的化疗敏感性预测及耐药逆转研究提供理论依据。

Nowadays, lung cancer is the most malignant tumor with the highest incidence and mortality in China. It is reported that TCRP1 was highly expressed in lung cancer comparing with the normal tissue, contributed to the development of lung cancer and mediated chemo-resistance of lung cancer to cDDP. However, the mechanism of transcriptional regulation of TCRP1 is unknown. The applicant found that p53 or acetylation transferase inhibitor could significantly down-regulated TCRP1. It is suggested that p53, TET2 and Hdac2 might interacted with each other by Tandem affinity chromatography and mass spectrometry assay. All these data indicated that p53/TET2/Hdac2 complex could down-regulated TCRP1 in lung cancer. To clarify this indication, we first intend to find the expression relationship of TCRP1, p53 and TET2 in lung cancer. Furthermore, the mechanism of p53/TET2/Hdac2 complex transcriptional regulating TCRP1 would be studied in lung cancer cell. Finally, the role of p53/TET2/Hdac2 complex transcriptional regulating TCRP1 was confirmed in node mice model and lung cancer tissues. Through the above study, we can elucidate the mechanism of transcriptional regulation in TCRP1, provide a new theoretical basis for the forecast and reversal of resistance to chemotherapy of lung cancer and clinical therapeutic targets.