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22 August 2018 : Laboratory Research  

High miR-718 Suppresses Phosphatase and Tensin Homolog (PTEN) Expression and Correlates to Unfavorable Prognosis in Gastric Cancer

Shufang Liu1AB, Ying Tian1EF, Chanchan Zhu2CD, Xiaoqing Yang3ABCDEFG*, Qing Sun3EFG

DOI: 10.12659/MSM.909527

Med Sci Monit 2018; 24: LBR5840-5850

Abstract

BACKGROUND: 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

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750