MicroRNA-183 promotes proliferation and invasion in oesophageal squamous cell carcinoma by targeting programmed cell death 4

L-H Ren, W-X Chen, S Li, X-Y He, Z-M Zhang, M Li, R-S Cao, B Hao, H-J Zhang, H-Q Qiu, R-H Shi
British Journal of Cancer 2014 November 11, 111 (10): 2003-13

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.

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