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

• Published in: British journal of cancer Vol. 111; no. 10; pp. 2003 - 2013
• Main Authors: Ren, L-H, Chen, W-X, Li, S, He, X-Y, Zhang, Z-M, Li, M, Cao, R-S, Hao, B, Zhang, H-J, Qiu, H-Q, Shi, R-H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11-11-2014; Nature Publishing Group
• Subjects: 631/337/384/331; 692/420/755; 692/699/67/1504/1477; Apoptosis; Apoptosis Regulatory Proteins - antagonists & inhibitors; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Base Sequence; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Blotting, Western; Cancer Research; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - secondary; Cell Adhesion; Cell death; Cell Movement; Cell Proliferation; Drug Resistance; Epidemiology; Esophageal Neoplasms - genetics; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - pathology; Esophagus; Esophagus - metabolism; Flow Cytometry; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; Lymphatic Metastasis; Medical sciences; MicroRNAs - genetics; Molecular Diagnostics; Molecular Medicine; Molecular Sequence Data; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Staging; Oncology; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Small Interfering - genetics; RNA-Binding Proteins - antagonists & inhibitors; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Sequence Homology, Nucleic Acid; Tumor Cells, Cultured; Tumors; oesophageal intraepithelial neoplasia; oesophageal squamous cell carcinoma; tumour progression; microRNA-183; programmed cell death 4; Cell proliferation; RNA interference; Targeting; Esophageal disease; Esophagus squamous cell carcinoma; Tumorous infiltration; Metastasis; Esophagus cancer; Cancerology; Tumor progression; Digestive system; Micro RNA; Malignant tumor; Invasion; Esophagus; Gene silencing; Cell death; Digestive diseases; Intraepithelial neoplasia; Cancer; Apoptosis
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2014.485

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.