Mir-483-5p promotes the malignant transformation of immortalized human esophageal epithelial cells by targeting HNF4A

MicroRNAs (miRNAs) are small non-coding RNAs that promote the progression of cancer by negatively regulating gene expression. Down-regulation of miR-483-5p was reported in a number of cancers. However, the biological functions of miR-483-5p in esophageal squamous cell carcinomas are not fully understood. In this study, the expression levels of miRNAs in the immortalized human esophageal epithelial cell line SHEE and the malignantly transformed esophageal carcinoma cell line SHEEC were examined by miRNA microarray chip. The expression level of miR-483-5p was verified by a quantitative reverse transcription-polymerase chain reaction. Growth, apoptosis, and colony formation ability were also examined in SHEEC cells after transfection with inhibitors targeting miR483-5p. And the target genes of miR-483-5p were predicted using bioinformatics approaches and the expression profile of SHEEC cells transfected with the miRNA inhibitors. Protein levels of the target gene in SHEEC cells with a control or miRNA inhibitors were measured using Western blotting. The expression of miR-483-5p was elevated in SHEEC cells as compared to the SHEE cells. Silencing of miR-483-5p expression in SHEEC cells inhibited both the proliferation and formation of colonies and increased apoptosis. We also identified hepatocyte nuclear factor 4α (HNF4A) as a target of miR-483-5p in SHEEC cells. Knockdown of HNF4A recapitulated the effects of miR-483-5p. Our data showed that the miR-483-5p/HNF4A axis affected the malignant transformation of immortalized human esophageal epithelial cells and is a potential therapeutic target for ESCC.