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Br J Cancer ; 111(10): 2003-13, 2014 Nov 11.
Article in English | MEDLINE | ID: mdl-25211657

ABSTRACT

BACKGROUND: Dysregulated microRNAs (miRNAs) can serve as oncogenes or suppressors and are associated with many cancers, including oesophageal squamous cell carcinoma (ESCC). METHODS: An alignment miRNA array was used to identify differentially expressed miRNAs in ESCC tissues. The expression of miR-183 and programmed cell death 4 (PDCD4) in oesophageal tissues from ESCC and early oesophageal carcinoma patients was examined by quantitative reverse transcriptase PCR and western blotting. A luciferase assay was performed to confirm miR-183 target genes. The effects of miR-183 on ESCC cells and the associated mechanisms were established by in vitro experiments. RESULTS: We identified 51 upregulated miRNAs and 17 downregulated miRNAs in our array, and miR-183 was one of the most upregulated miRNAs. An inverse correlation between miR-183 and PDCD4 levels was found in ESCC tissues. Upregulated expression of miR-183 was not correlated with tumour stage or lymphatic metastasis in ESCC patients. The luciferase assay confirmed that miR-183 directly interacted with the PDCD4 mRNA 3'-untranslated region in ESCC cells. Overexpression of miR-183 led to decreased PDCD4 protein levels and promoted ESCC cell proliferation and invasion. Inhibition of the PI3K/Akt signalling pathway increased PDCD4 protein levels and decreased miR-183 expression in ESCC cells. CONCLUSIONS: MiR-183 promotes ESCC cell proliferation and invasion by directly targeting PDCD4, which suggests that it is involved in the pathogenesis of ESCC.


Subject(s)
Apoptosis Regulatory Proteins/metabolism , Carcinoma, Squamous Cell/secondary , Cell Movement , Cell Proliferation , Esophageal Neoplasms/pathology , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , RNA-Binding Proteins/metabolism , Apoptosis , Apoptosis Regulatory Proteins/antagonists & inhibitors , Apoptosis Regulatory Proteins/genetics , Base Sequence , Blotting, Western , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Cell Adhesion , Esophageal Neoplasms/genetics , Esophageal Neoplasms/metabolism , Esophagus/metabolism , Flow Cytometry , Humans , Immunoenzyme Techniques , Lymphatic Metastasis , Molecular Sequence Data , Neoplasm Staging , RNA, Messenger/genetics , RNA, Small Interfering/genetics , RNA-Binding Proteins/antagonists & inhibitors , RNA-Binding Proteins/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Sequence Homology, Nucleic Acid , Tumor Cells, Cultured
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