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 a recent study by researchers from Henan University of Science and Technology, 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.

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 miR-483-5p. 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. They 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.

This 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.

HNF4A is a direct target of miR-483-5p. miR-483-5p
binding sites in the HNF4A 3’UTR region

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A Western blot analysis demonstrated that the transfection of miR-483-5p reduced HNF4A protein expression (A). HNF4A mutation indicates the HNF4A 3’UTR with a mutation in miR-483-5p binding sites (B). Relative luciferase assay comparing the pGL3-HNF4A and pGL3-HNF4A mutation vectors in SHEEC cells. Firefy luciferase activity was normalized to Renilla luciferase activity (C). Values are expressed as the mean ± standard deviation. *P<0.05 vs. control.


J. Sun, X. Li, W. Wang, W. Li, S. Gao, J. Yan (2017) Mir-483-5p promotes the malignant transformation of immortalized human esophageal epithelial cells by targeting HNF4A Int. J. Clin. Exp. Pathol. 10(9):9391-9399 [article]

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