Aberrant methylation-mediated downregulation of long noncoding RNA LOC100130476 correlates with malignant progression of esophageal squamous cell carcinoma.

BACKGROUND: Dysregulated long non-coding RNAs (lncRNAs) are involved in many complicated human diseases including cancer. AIMS: To determine the role and methylation status of a new lncRNA LOC100130476 in the pathogenesis of esophageal squamous cell carcinoma (ESCC).
METHODS: One hundred and twenty three ESCC patients with tumor tissues and corresponding adjacent normal tissues were enrolled. The expression level and methylation status of LOC100130476 in esophageal cancer cell lines and primary ESCC samples were respectively detected.
RESULTS: Significant downregulation of LOC100130476 was detected in esophageal cancer cell lines and primary ESCC tumor tissues. Up-regulation of LOC100130476 led to the inhibition of proliferation and invasiveness of the cancer cells. Aberrant hypermethylation of the CpG sites in exon 1 closing to the transcription start site was found to be more tumor-specific and to be more critical for gene silencing. Hypermethylation of these CpG sites was associated with TNM stage and pathological differentiation. ESCC patients in stage III and IV, with low expression or hypermethylation of the CpG sites in exon 1 demonstrated poor patient survival.
CONCLUSIONS: LOC100130476 is down-regulated in ESCC at least partly by hypermethylation of CpG sites in exon 1 and its hypermethylation may have prognostic implications for ESCC patients.