目的 探讨长链非编码RNA LINC00261在Barrett食管、食管腺癌组织中的表达及其可能作用机制。 方法 利用qRT-PCR检测LINC00261在中国人群正常食管鳞状上皮、Barrett食管及食管腺癌组织标本中的表达水平变化。并建立了以人胚胎干细胞为细胞模型。 结果 在Barrett食管及食管腺癌组织标本中,LINC00261表达较正常食管鳞状上皮组织均显著上调(P〈0.01);酸暴露及胆酸可诱导人胚胎干细胞LINC00261表达显著上调并抑制FOXA2蛋白表达水平(P〈0.05),而LINC00261慢病毒载体转染亦可诱导FOXA2蛋白表达水平下调;上调FOXA2表达可阻断人胚胎干细胞在酸暴露及胆酸诱导下CDX2表达及细胞分化表型(柱状上皮标志物MUC2表达)的变化。 结论 LINC00261在Barrett食管的发生过程中发挥关键作用,其可能通过抑制FOXA2表达参与相关调控。
Objective To evaluate the expression of long non-coding RNA, LINC00261, in Barrett’s esophagus and esophageal adenocarcinoma, and to investigate its possible mechanism. Methods qRT-PCR was used to analyze the expression levels of LINC00261 in normal esophageal squamous epithelium, Barrett’s esophagus and esophageal adenocarcinoma of Chinese population. The possible role of LINC00261 in the development of Barrett’s esophagus was investigated in human embryonic stem cells. Results The expression level of LINC00261 were significantly higher in the Barrett’s esophagus and esophageal adenocarcinoma than the normal esophageal squamous epithelium tissues (P〈0.01). Acid and bile exposure enhanced the expression of LINC00261 and inhibited the protein level of FOXA2 in human embryonic stem cells. While lentivirus-mediated up-regulation of LINC00261 also induced the inhibition of FOXA2 expression. What’s more, FOXA2 up-regulation blocked the expression of CDX2 and differentiation phenotype (expression of MUC2, a biomarker for columnar differentiation) in human embryonic stem cells induced by acid and bile exposure. Conclusion LINC00261 plays a key role in the development of Barrett’s esophagus, and FOXA2 is involved in the related regulation by inhibiting FOXA2.