High miR-718 Suppresses Phosphatase and Tensin Homolog (PTEN) Expression and Correlates to Unfavorable Prognosis in Gastric Cancer
Shufang Liu, Ying Tian, Chanchan Zhu, Xiaoqing Yang, Qing Sun
Department of Clinical Laboratory, Linyi Central Hospital, Linyi, Shandong, China (mainland)
Med Sci Monit 2018; 24:5840-5850
Phosphatase and tensin homolog (PTEN) is a kind of phosphatase which has been demonstrated to suppress progression of gastric cancer. Many micro-RNAs (miRNAs), such as miR-106b, miR-93, and miR-200c, could inhibit expression of PTEN in cell lines; and many miRNAs including miR-21, miR-22, miR-18a, and miR-222 are related to the progression and prognosis of gastric cancer. However, among these miRNAs, the clinical significance of miR-718 has not yet been elucidated.
MATERIAL AND METHODS: The expression of PTEN and miR-718 in 141 gastric cancer tissues were detected by immunohistochemistry and quantitative real-time PCR respectively. The correlation between PTEN, miR-718, and the clinicopathological factors was analyzed by χ² test. The prognostic significance of PTEN and miR-718 was evaluated by univariate and multivariate analysis. Luciferase reporter assay was performed to evaluate the regulation of PTEN by miR-718. The effect of miR-718 on gastric cancer proliferation and invasion was investigated by MTT assay and Transwell assay.
RESULTS: Low expression of PTEN and high expression of miR-718 were both significantly associated with unfavorable prognosis, and both were identified as biomarkers predicting poorer prognosis of patients with gastric cancer. Increased miR-718 expression could decrease PTEN expression, thus enhancing phosphatidylinositide 3-kinases/protein kinase B (PI3K/Akt) signaling. Moreover, the abilities of proliferation and invasion of gastric cells transfected with miR-718 were promoted significantly compared with those transfected with control miRNA.
CONCLUSIONS: Low expression of PTEN and increased expression of miR-718 in gastric cancer tissues were both independent unfavorable prognostic factors of gastric cancer. Upregulation of miR-718 could increase PI3K/Akt signaling by directly downregulating PTEN, thus promoting the proliferation and invasion of gastric cancer cells.
Keywords: Prognosis, PTEN Phosphohydrolase, Stomach Neoplasms