Aberrant Methylation-mediated Silencing of lncRNA MEG3 Functions as a ceRNA in Esophageal Cancer.

Abstract

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 down-regulation 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. Up-regulation 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. Up-regulation of miR-9 was detected in esophageal cancer cell lines and ESCC tissues, and miR-9 promoted esophageal cancer cell proliferation and invasion. Finally, down-regulation and hypermethylation of MEG3 was associated with ESCC patients' survival.