Abstract
Epithelial-to-mesenchymal transition (EMT) is believed to be associated with cancer cell malignancy, and also to cause cancer invasion and metastasis. Recent evidence indicates that small non-protein coding RNA [microRNAs (miRNAs/miRs)] may act as powerful regulators of EMT. The present study aimed to systematically delineate miR-503 expression in gastric cancer and analyse the function of miR-503 in gastric cancer EMT. In the present study, miR-503 expression was detected in gastric cancer cell lines and gastric cancer tissues by quantitative polymerase chain reaction. Gastric cancer cell migration, invasion and proliferation capabilities were analysed by Transwell, MTT and clonability assays. The expression of mesenchymal markers, including fibronectin, vimentin, N-cadherin, SNAIL and the epithelial marker, E-cadherin, was examined by immunoblot analysis following miR-503 transfection. miR-503 expression was found to be reduced in gastric cancer cell lines compared with normal gastric mucosa cell lines, and the expression of miR-503 was upregulated in non-metastatic-derived gastric cancer cell lines compared with metastatic-derived lines. miR-503 expression levels were significantly reduced in tumour tissues in comparison with adjacent normal mucosa tissues, and the miR-503 expression levels in patients with metastases were significantly lower than those in patients without. miR-503 inhibited gastric cancer cell migration, invasion and proliferation. Fibronectin, vimentin, N-cadherin and SNAIL protein levels were decreased, but E-cadherin expression was increased in an AGS cell line transfected with miR-503. Taken together, the present findings indicate that miR-503 acts as a novel tumour suppressor gene in gastric cancer and can inhibit EMT in gastric cancer cells.
Highlights
MicroRNAs are non‐coding RNA molecules, 21‐23 nucleotides long, that regulate gene expression at the post‐transcriptional level [1,2,3]. miRNA expression profiling analyses have revealed a global downregulation of mature miRNA levels in primary human tumours relative to normal tissues [4,5]
epithelial‐to‐mesenchymal transition (EMT) is regulated by a variety of signalling pathways that originate from the stroma that surrounds cancer cells; these pathways are activated by cytokines, including transforming growth factor‐β (TGFβ), hepatocyte growth factor, platelet‐derived growth factor, epidermal growth factor and integrin engagement, all of which converge at the level of key transcription factors, ZEB, SNAIL and TWIST [6]
To investigate the miR‐503 expression levels in human gastric cancer cell lines, expression was monitored in several cancer cell lines (SGC7901, HGC27, AGS, MKN45, NCI‐N87 and MGC80‐3) and a normal gastric mucosa cell line (GES1). miR‐503 expression was reduced in the gastric cancer cell lines compared with the normal gastric mucosa cells
Summary
MicroRNAs (miRNAs/miRs) are non‐coding RNA molecules, 21‐23 nucleotides long, that regulate gene expression at the post‐transcriptional level [1,2,3]. miRNA expression profiling analyses have revealed a global downregulation of mature miRNA levels in primary human tumours relative to normal tissues [4,5]. MicroRNAs (miRNAs/miRs) are non‐coding RNA molecules, 21‐23 nucleotides long, that regulate gene expression at the post‐transcriptional level [1,2,3]. MiRNAs may function as tumour suppressors or oncogenes, and dysregulated miRNA expression may contribute to tumour cell metastasis. Metastasis is a complex, multi‐step and dynamic biological event, and a critical process in the metastatic cascade is the epithelial‐to‐mesenchymal transition (EMT). EMT is regulated by a variety of signalling pathways that originate from the stroma that surrounds cancer cells; these pathways are activated by cytokines, including transforming growth factor‐β (TGFβ), hepatocyte growth factor, platelet‐derived growth factor, epidermal growth factor and integrin engagement, all of which converge at the level of key transcription factors, ZEB, SNAIL and TWIST [6]. One area of significant progress has been the identification of the critical roles of miRNAs in these processes
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