Dong Zhiming, Zhang Aili, Liu Shengnan, Lu Fan, Guo Yanli, Zhang Guoqiang, Xu Fenglou, Shi Yabin, Shen Supeng, Liang Jia, Guo Wei
Laboratory of Pathology, Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Surgery Department, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Mol Cancer Res. 2017 Jul;15(7):800-810. doi: 10.1158/1541-7786.MCR-16-0385. Epub 2017 May 24.
Maternally expressed gene 3 (MEG3), a long non-coding RNA (lncRNA), has tumor-suppressor properties and its expression is lost in several human tumors. However, its biological role in esophageal squamous cell carcinoma (ESCC) tumorigenesis is poorly defined. The present study determined the role and methylation status of MEG3 in esophageal cancer cells and ESCC clinical specimens, and further observed the competing endogenous RNA (ceRNA) activity of MEG3 in the pathogenesis and development of ESCC. Significant downregulation of MEG3 was detected in esophageal cancer cells and ESCC tissues and the expression level of MEG3 was significantly increased in cancer cells after treated with the DNA methyltransferase inhibitor 5-Aza-dC. Upregulation of MEG3 led to the inhibition of proliferation and invasiveness of the cancer cells. The aberrant promoter hypermethylation of MEG3 indicates silencing of its expression. Furthermore, MEG3 acts as a ceRNA to regulate the expression of E-cadherin and FOXO1 by binding hsa-miR-9. Upregulation of miR-9 was detected in esophageal cancer cell lines and ESCC tissues, and miR-9 promoted esophageal cancer cell proliferation and invasion. Finally, downregulation and hypermethylation of MEG3 was associated with ESCC patients' survival. MEG3 functions as a tumor-suppressive lncRNA and aberrant promoter hypermethylation is critical for MEG3 gene silencing in ESCC. In addition, MEG3 acts as a ceRNA to regulate expression of E-cadherin and FOXO1 by competitively binding miR-9 and may be used as a potential biomarker in predicting ESCC patients' progression and prognosis. .
母系表达基因3（MEG3）是一种长链非编码RNA（lncRNA），具有肿瘤抑制特性，其表达在几种人类肿瘤中缺失。然而，其在食管鳞状细胞癌（ESCC）发生中的生物学作用尚不清楚。本研究确定了MEG3在食管癌细胞和ESCC临床标本中的作用及甲基化状态，并进一步观察了MEG3在ESCC发病机制和发展中的竞争性内源RNA（ceRNA）活性。在食管癌细胞和ESCC组织中检测到MEG3显著下调，在用DNA甲基转移酶抑制剂5-氮杂-2'-脱氧胞苷（5-Aza-dC）处理后，癌细胞中MEG3的表达水平显著升高。MEG3上调导致癌细胞增殖和侵袭受到抑制。MEG3启动子异常高甲基化表明其表达沉默。此外，MEG3作为ceRNA通过结合hsa-miR-9来调节E-钙黏蛋白和FOXO1的表达。在食管癌细胞系和ESCC组织中检测到miR-9上调，且miR-9促进食管癌细胞增殖和侵袭。最后，MEG3下调和高甲基化与ESCC患者的生存相关。MEG3作为一种肿瘤抑制性lncRNA发挥作用，启动子异常高甲基化对ESCC中MEG3基因沉默至关重要。此外，MEG3作为ceRNA通过竞争性结合miR-9来调节E-钙黏蛋白和FOXO1的表达，可能作为预测ESCC患者病情进展和预后的潜在生物标志物。
