Downregulation of LINC00886 facilitates epithelial-mesenchymal transition through SIRT7/ELF3/miR-144 pathway in esophageal squamous cell carcinoma.

Abstract

LINC00886 has been reported to be down-regulated in laryngeal squamous cell carcinoma, and aberrant DNA methylation status of it has been screened in several tumor types. However, the roles of LINC00886 in esophageal squamous cell carcinoma (ESCC) remained unclarified. The present study was to investigate the expression level, epigenetic inactivation mechanisms, and functions of LINC00886 in ESCC tumorigenesis. Frequent down-regulation of LINC00886 was verified in esophageal cancer cells and ESCC tissues. There are CpG islands spanning the promoter and exon 1 regions of LINC00886 gene, and DNA hypermethylation of proximal promoter led to transcriptional inhibition of LINC00886, moreover, histone modification also played certain roles in LINC00886 transcription. LINC00886 functioned as a tumor suppressor by inhibiting proliferation, migration, and invasion of esophageal cancer cells. LINC00886 was down-regulated following TGF-β1 treatment in esophageal cancer cells and participated in epithelial-mesenchymal transition (EMT) process by regulating EMT-related genes, especially ZEB1 and ZEB2. ELF3 was proved to be one of the downstream target genes of LINC00886. LINC00886 may interact with and recruit SIRT7 to decrease acetylation level of H3K18 on the promoter region of ELF3 to inhibit its expression. Furthermore, ELF3 may promote EMT process via promoting ZEB1 and ZEB2 expression through binding to the promoter region of miR-144 to suppress miR-144-3p transcriptional activity in ESCC. These data suggest that LINC00886 may act as a tumor suppressor gene in ESCC and its down-regulation through epigenetic mechanisms promotes EMT process via SIRT7/ELF3/miR-144 pathway in ESCC. Thus, LINC00886 may be a potential therapeutic target for ESCC treatment.