长链非编码RNA LINC01198在TGF-β 诱导的食管癌细胞上皮间质转化中的作用及分子调控机制

上皮-间质转化（EMT）在食管癌的侵袭转移中起重要作用，TGF-β是 EMT 的重要启动因子。我们已对TGF-β/Smads通路在食管鳞癌中的作用进行了系统研究，发现TGF-β1诱导食管癌细胞系发生EMT后长链非编码RNA LINC01198的表达明显升高，生物信息学分析及前期研究发现其有可能通过多种机制参与食管鳞癌的侵袭转移。本研究通过探讨LINC01198在食管鳞癌侵袭转移中的生物学作用，检测其是否通过引导DNMT、EZH2、EHMT2等在CDH1、WWOX、FBXO32等的启动子区聚集从而调控它们的甲基化及转录，分析其是否作为竞争性内源RNA（ceRNA）通过与miR-124等的竞争性结合从而调控SNAI2、ZEB1、ZEB2等的表达，并对TGF-β1诱导的LINC01198高表达机制进行探索，将为阐明食管癌的侵袭转移机制提供有力的实验数据，有望为食管癌的治疗和预后判断提供分子靶点。

Epithelial-mesenchymal transition (EMT) plays an important role in the invasion and metastasis of esophageal cancer and TGF-β is an important initiation factor for EMT. We have studied the role of TGF-β/Smads pathway in esophageal squamous cell carcinoma (ESCC), and found significant upregulation of long noncoding RNA LINC01198 in TGF-β1 treated esophageal cancer cell lines. Bioinformatics analysis and preliminary experiments demonstrated that LINC01198 may involve in the invasion and metastasis of ESCC through various mechanisms. The present study was to investigate the biological effects of LINC01198 in invasion and metastasis of ESCC, detect whether LINC01198 guides DNMT, EZH2, EHMT2 to accumulate in the promoter region of CDH1, WWOX and FBXO32 to regulate the methylation status and transcription of these genes, analyze whether LINC01198 acts as the competitive endogenous RNA (ceRNA) to regulate the expression of SNAI2, ZEB1, ZEB2 by competitive binding with miR-124, further explore the mechanisms of TGF-β1 induced upregulation of LINC01198, in order to offer powerful experimental data for elucidating the mechanisms of invasion and metastasis of ESCC, and provide valuable molecular target for treatment and prognosis of ESCC.