MicroRNA-197 inhibits gastric cancer progression by directly targeting metadherin

2017 
Gastric cancer is the fifth most frequent malignancy and the fourth most common cause of cancer‑associated mortality worldwide. MicroRNAs (miRNAs) are a group of small RNAs that regulate several cellular processes. In particular, a large number of miRNAs are involved in gastric cancer formation and progression. Thus, miRNAs may be considered as effective diagnostic biomarkers and therapeutic methods for gastric cancer. The aim of the current study was to detect miRNA (miR)‑197 expression in gastric cancer and to investigate its biological role and associated mechanism in gastric cancer. In the present study, miR‑197 expression was demonstrated to be considerably downregulated in gastric cancer tissues and cell lines. Its low expression level was associated with tumour size, invasive depth, tumour‑node‑metastasis staging and lymph node metastasis. High expression of miR‑197 inhibited tumour cell proliferation and invasion in vitro. Subsequently, metadherin (MTDH) was identified as a direct target gene of miR‑197 in gastric cancer, and this was confirmed by bioinformatics analysis, Dual‑luciferase reporter assay, reverse transcription quantitative polymerase chain reaction and western blot analysis. MTDH expression was upregulated in gastric cancer and was inversely correlated with miR‑197 expression levels. In addition, MTDH overexpression prevented the proliferation and inhibited invasion induced by miR‑197 overexpression. In addition, miR‑197 was demonstrated to regulate the phosphatase and tensin homolog (PTEN)/AKT signalling pathway in gastric cancer. The results of the present study suggested that miR‑197 serves a tumour‑suppressing role in human gastric carcinogenesis and progression by regulating the MTDH/PTEN/AKT signalling pathway. The miR‑197/MTDH axis may provide a novel effective therapeutic target for patients with gastric cancer.
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