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. .

Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play important roles in several biological processes and dysregulated lncRNAs are involved in different kinds of cancer and are associated with carcinogenesis, metastasis, and prognosis of cancer. The role of a new lncRNA LOC100130476 in gastric cardia adenocarcinoma (GCA) has remained unknown. The present study investigated the role and methylation status of LOC100130476 in the pathogenesis of GCA, and further evaluated the potential prognostic role of LOC100130476 in GCA. Significant downregulation of LOC100130476 was detected in SGC-7901 and BGC-823 cell lines and primary GCA tissues. Methylation frequency of LOC100130476 was gradually increased from exon 1 to exon 2 both in tumor tissues and corresponding normal tissues; however, methylation status of region 1 closing to the transcription start site was more tumor-specific among the three regions examined. The findings of the association between LOC100130476 expression, methylation and TNM stage, pathological differentiation, and GCA patients' survival further identified the role of LOC100130476 as a tumor suppressor gene. Furthermore, the hypermethylation of LOC100130476 was also detected in peripheral white blood cells of GCA cases. Thus, LOC100130476 may be act as a tumor suppressor gene in GCA carcinogenesis and aberrant methylation at the CpG sites near the transcription start site within exon 1 may be critical for gene silencing. In addition, aberrant methylation of LOC100130476 in peripheral white blood cells and GCA tissues may be used as a potential valuable biomarker in GCA diagnosis and prognosis.

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