目的：探究核受体辅阻遏物2（NCOR2）基因对食管鳞状细胞癌（ESCC）发生发展的影响及其潜在的分子调控机制。方法: 收集2017 年5月至2018 年7月间在山西省肿瘤医院确诊的155 例ESCC 患者的癌及癌旁组织标本及临床资料，利用患者的转录组和临床病理数据进行生存预后分析及临床关联性分析。采用qPCR 法检测6 种ESCC 细胞（TE-1、TE-5、TE-9、 KYSE150、KYSE180 和KYSE450）中NCOR2基因的表达水平，筛选NCOR2基因高表达的KYSE450 细胞进行siRNA 敲低实验，构建敲降NCOR2的细胞模型。利用CCK-8、克隆形成、细胞划痕和Transwell 实验检测敲低NCOR2对 KYSE450 细胞增殖活性、克隆形成、迁移和侵袭能力的影响。对NCOR2 敲低的KYSE450 细胞进行转录组测序分析，筛选差异表达基因，进行GO 和KEGG富集分析，解析NCOR2可能影响的信号调控网络。结果：NCOR2在ESCC组织中表达水平显著高于癌旁组织（P<0.01），NCOR2高表达ESCC 患者的预后较差（P<0.05）。敲低NCOR2基因表达后，KYSE450 细胞划痕愈合率、迁移和侵袭能力均显著降低（均P<0.01），对细胞的增殖活力及克隆形成能力均无显著影响（均P>0.05）。在KYSE450 细胞中敲低NCOR2基因后，转录组测序分析后发现54个基因发生了显著上调、127 个基因发生了显著下调。KEGG分析发现，显著差异基因富集于PI3K/AKT分子信号通路（P<0.01），该通路中的4个基因PIK3R3、IL4R、COL1A1、EFNA1的表达水平在155 例ESCC患者临床样本的转录组数据中与NCOR2呈显著正相关（均P<0.01），与转录组测序结果相吻合。结论：NCOR2可以通过影响PI3K/AKT 信号通路并促进KYSE450细胞迁移与侵袭，进而影响ESCC的发生与发展。

Objective: To explore the role of nuclear receptor corepressor 2 (NCOR2) gene in the carcinogenesis and progression of esophageal squamous cell carcinoma (ESCC) and investigate its underlying molecular regulatory mechanism. Methods: Tumor tissue specimens, adjacent tissue specimens and clinical data of 155 ESCC patients diagnosed in Shanxi Tumor Hospital between May 2017 and July 2018 were collected. Transcriptome and clinicopathological data of patients were used for survival prognosis analysis and clinical association analysis. qPCR assay was conducted to detect the expression levels of NCOR2 gene in six ESCC cell lines (TE-1,TE-5, TE-9, KYSE150, KYSE180 and KYSE450). KYSE450 cells with highly-expressed NCOR2 gene were selected for siRNA knockdown experiment and construction of knockdown NCOR2 cell model. CCK-8 cell viability assay, colony formation assay, wound healing assay and Transwell assay were performed to explore the effect of NCOR2 knockdown on proliferation vitality, clone formation, invasion and migration abilities of KYSE450 cells. Transcriptome sequencing analysis was conducted on NCOR2 knockdown KYSE450 cells to identify differentially expressed genes. GO (Gene Ontology, GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes, KEGG) analysis were performed to characterize the signal regulation network that might be affected by NCOR2.Results: The expression of NCOR2 in ESCC tumor tissues was significantly higher than that in the adjacent tissues (P<0.01). Poor prognosis were associated with higher expression of NCOR2 in ESCC patients (P<0.05). The knocking-down of NCOR2 significantly reduced wound healing rate and cell migration and invasion abilities of KYSE450 cells (all P<0.01). However, cell proliferation and colony formation abilities were not significantly affected (all P>0.05). After NCOR2 knockdown in KYSE450 cells, transcriptome sequencing analysis revealed that 54 genes were significantly up-regulated and 127 genes were significantly down-regulated. KEGG analysis results showed that the significantly differentially expressed genes were enriched in PI3K/AKT signaling pathway (P<0.01). In the transcriptome data of the clinical samples of the 155 ESCC patients, the expression levels of the 4 genes PIK3R3, IL4R, COL1A1 and EFNA1 of the PI3K/AKT pathway were significantly correlated with NCOR2 (all P<0.01), which was consistent with the transcriptome sequencing analysis results. Conclusion: NCOR2 can promote the invasion and migration of KYSE450 cells via the PI3K/AKT signaling pathway, thus affecting ESCC carcinogenesis and progression.

山西省博士启动基金（No. SD2033）；山西医科大学引进人才启动基金