目的：检测食管鳞状细胞癌（esophageal squamous cell carcinoma, ESCC）中长链非编码RNA XLOC_008370（long non-colding RNA XLOC_008370, lncRNA XLOC_008370）的表达及其甲基化状态，探讨XLOC_008370在ESCC发生及发展中的作用机制。方法：分别应用RT-PCR以及甲基化特异性PCR（methylation specific PCR, MSP）法检测DNA甲基化转移酶抑制剂5-氮杂-2’-脱氧胞苷（5-Aza-2’-deoxycitydine, 5-Aza-dC）处理前后的ESCC细胞系（TE1、TE13、Eca109、T.TN、YES-2）以及ESCC组织及相应癌旁正常组织中XLOC_008370的表达和甲基化状态，分析其与临床病理特征的关系。结果：5种ESCC细胞中XLOC_008370的表达均呈阴性或弱阳性，经5-Aza-dC处理后，5种细胞中XLOC_008370的表达均升高。5种细胞中XLOC_008370基因呈高甲基化状态，应用5-Aza-dC处理后，Eca109、Yes-2细胞中XLOC_008370基因甲基化程度降低，非甲基化程度增加，其余3种细胞中XLOC_008370基因均表现为非甲基化状态。XLOC_008370在ESCC组织中的表达显著低于癌旁正常组织（P<0.05），并与TNM分期和组织学分化程度密切相关（P<0.05）。ESCC组织中XLOC_008370的启动子区甲基化率为(54.02%, 47/87），显著高于癌旁正常组织（9.20%, 8/87）（P<0.05），并与TNM分期和组织学分化程度密切相关（P<0.05）。发生XLOC_008370甲基化的ESCC组织中XLOC_008370的表达显著低于未发生甲基化的ESCC组织（P<005）。结论： XLOC_008370的异常低表达可能与ESCC的发生密切相关，且其启动子区甲基化可能是导致其表达沉默的机制之一。

Objective:To investigate the expression and methylation status of lncRNA XLOC_008370 gene in esophageal squamous cell carcinoma（ESCC）and explore their role in ESCC development. Methods: RT-PCR and methylation specific PCR (MSP) were used to examine the expression and methylation status of XLOC_008370 gene in esophageal cancer cell lines (TE1, TE13, T.TN, Eca109, Yes-2) and in primary ESCC tissues. Their relationships with clinical pathological feature were further analyzed.Results: All 5 lines of esophageal cancer cells express no or low level of XLOC_008370, which was increased significantly after exposed to 5-Aza-dC, a DNA methyltransferase inhibitor. While the XLOC_008370 gene was highly methylated in all the 5 lines of cells, treatment with 5-Aza-dC led to decreased methylation of the gene in the Eca109 and Yes-2 cells, and completely demethylation in the TE1, TE13, and T.TN cells. In primary ESCC tumor tissues, the level of XLOC_008370 was significantly lower compared to that in corresponding non-cancerous tissues (P<0.05), and the expression was associated with TNM and pathological stages (P<0.05). The methylation frequency of XLOC_008370 gene promoter in ESCC tissues (54.02%, 47/87) was significantly higher than that in corresponding normal tissues (9.20%, 8/87) (P<0.05), and it was also associated with TNM and pathological stages (P<0.05). Furthermore, the level of XLOC_008370 in ESCC tumor tissues having its gene methylated was significantly lower than that in tumor tissues having the gene unmethylated (P<0.05). Conclusion: 〗Aberrant low expression of lncRNA XLOC_008370 is closely related to the development of ESCC, and promoter methylation is likely one of the mechanisms responsible for its decreased expression.

河北省科技计划资助项目（No.122777117）；河北省医学研究重大专项资助（冀财预复\[2012\]2056号）