组蛋白修饰相关基因MTA3通过长非编码RNA SOX2OT调控食管鳞癌细胞可塑性

肿瘤细胞可塑性能够促进EMT并增强肿瘤细胞干性，是肿瘤耐药，转移和复发的根源,但调节机制不明。前期工作表明：炎症因子诱导食管鳞癌（ESCC）细胞可塑性；转移相关蛋白3（MTA3）和ESCC细胞可塑性密切相关；MTA3和其功能伴侣组蛋白去乙酰化酶（HDAC）均参与调节肿瘤干性相关的长非编码RNA (lncRNA) SOX2OT的表达。据此提出假说：MTA3通过SOX2OT调控ESCC肿瘤细胞可塑性；MTA3通过组蛋白去乙酰化调节SOX2OT的转录。本研究拟①应用炎症诱导模型，在体外和体内水平，并结合临床标本和生物信息，确认MTA3抑制ESCC细胞可塑性；②在体外和体内水平验证SOX2OT介导MTA3对ESCC细胞可塑性的调控；③在分子水平探讨MTA3通过组蛋白去乙酰化抑制SOX2OT转录。课题以我国高发的食管鳞癌为研究对象，旨在探索肿瘤细胞可塑性的作用和关键调控通路，为治疗肿瘤提供新的思路。

Cancer cell plasticity gives rise to the acquisition of cancer stemness and induces epithelial-mesenchymal transition (EMT), which drives metastasis, progression and drug resistance. However, the underlying mechanism is unclear. Our preliminary data showed that cytokine induces cell plasticity in esophageal cell squamous carcinoma (ESCC), metastatic tumor antigen 3 (MTA3) is closely associated with cancer cell plasticity, and both MTA3 and its functional partner HDAC are involved in the repression of long noncoding RNA (lncRNA) SOX2OT. We reasoned that MTA3 regulates ESCC cell plasticity via repression of SOX2OT transcription in a HDAC dependent manner. We thus first set to clarify the MTA3's regulation on ESCC cell plasticity using cultured cells, animal model, patient specimen and bioinformatic data mining. Second, we will verify that SOX2OT mediates MTA3's regulation on ESCC cell plasticity. Third, we will elucidate that MTA3 represses the transcription of SOX2OT in a HDAC dependent manner. ESCC is highly incident in China. The project is of importance for the insight of regulatory mechanism on cancer cell plasticity, and is favorable to design the novel anti-cancer therapeutic strategy.