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

1] Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, Nanjing 210029, PR China [2] Department of Gastroenterology, Zhangjiagang First People's Hospital, Affiliated Hospital of Soochow University, Jiangsu Province, Suzhou 215006, PR China.
2014-5-23; doi: 10.1038/bjc.2014.485
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.





PMID:25211657






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