OncoTargets and Therapy (Jun 2019)

miR-3691-5p promotes hepatocellular carcinoma cell migration and invasion through activating PI3K/Akt signaling by targeting PTEN

  • Du W,
  • Zhang X,
  • Wan Z

Journal volume & issue
Vol. Volume 12
pp. 4897 – 4906

Abstract

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Wei Du,1,* Xu Zhang,1,* Zhen Wan21Department of Clinical Medicine, School of Queen Mary, Nanchang University, Nanchang, 330006, People’s Republic of China; 2Department of General Surgery, the First Affiliated Hospital of Nanchang University, Nanchang 33006, People’s Republic of China*These authors contributed equally to this work Background: The enhanced ability of cancer metastasis is the major cause for the cancer-related death of hepatocellular carcinoma (HCC). Better understanding the mechanisms for the motility of cancer cells will benefit the treatment. Accumulating evidence suggests that aberrant microRNA (miRNA) expression contributes to HCC development and progression, whereas miR-3691-5p has not been reported in HCC.Purpose: The aim of this study was to elucidate the expression, function and mechanism of miR-3691-5p in HCC.Methods: Real-time quantitative polymerase chain reaction (qPCR) was performed to detect miR-3691-5p expression in HCC tissues and cell lines database analysis were conducted for detection of the expression of miR-3691-5p in HCC. Then, the association of miR-3691-5p with clinicopathological features of HCC patients were statistically measured. Subsequently, we attempted to observe the effects of miR-3691-5p on migration and invasion of HCC cells by transwell assays. Furthermore, bioinformatics tools and luciferase reporter gene assay as well as recuse experiments were conducted to explore the target of miR-3691-5p in HCC, and to explore whether the target mediated the effects of miR-3691-5p HCC cells.Results: In the current study, we found that miR-3691-5p expression was elevated in both HCC tissues and cell lines, which was significantly correlated with poor prognosis and clinicopathological features including TNM stage (P=0.016) and vascular invasion (P=0.016). Furthermore, gain-or loss-of function assays demonstrated that miR-3691-5p promoted HCC cell migration and invasion. Luciferase reporter assay confirmed that PTEN was a direct downstream target of miR-3691-5p. Recuse assays showed that restoration of PTEN reversed the effects of miR-3691-5p on HCC cell migration and invasion through decreasing PI3K/Akt signaling.Conclusion: Our results demonstrated that miR-3691-5p contributes to HCC cell migration and invasion through activating PI3K/Akt signaling by targeting PTEN.Keywords: miR-3691-5p, hepatocellular carcinoma, PTEN, PI3K/Akt, migration, invasion

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