OncoTargets and Therapy (2020-09-01)

MicroRNA-6071 Suppresses Glioblastoma Progression Through the Inhibition of PI3K/AKT/mTOR Pathway by Binding to ULBP2

  • Zhou Y,
  • An H,
  • Wu G

Journal volume & issue
Vol. Volume 13
pp. 9429 – 9441

Abstract

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Yunyan Zhou,1,* Hongwei An,2,* Gang Wu3 1Second Department of Neurology, Rongcheng People’s Hospital, Shandong Province, Rongcheng, Shandong 264300, People’s Republic of China; 2Surgery of Lingcheng, Hospital of Traditional Chinese Medicine in Dezhou City, Dezhou, Shandong 253500, People’s Republic of China; 3Department of Neurology, Yan’an Hospital of Kunming, Kunming, Yunnan 650051, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gang Wu Email [email protected]: The purpose of this study was to explore the effect of microRNA-6071 (miR-6071) on glioblastoma (GBM) and its potential mechanisms.Methods: In this study, the expressions of miR-6071 and UL16 binding protein 2 (ULBP2) were measured by qRT-RCR in GBM tissues and cells. The prognostic values of miR-6071 and ULBP2 were evaluated by Kaplan–Meier methods using the data obtained from The Cancer Genome Atlas (TCGA) database. The cell clones, proliferation, apoptosis, migration and invasion in GBM cells were detected by colony formation assay, EdU assay, flow cytometry, wound-healing assay and transwell assay. The targeting relationship between miR-6071 and ULBP2 was predicted by Targetscan 7.2 and further verified by dual-luciferase reporter gene assay. Moreover, the expressions of Bax, caspase-3, Bcl-2, matrix metalloproteinases 2 (MMP-2), MMP-9, phosphatidylinositol 3′-kinase (PI3K), p-PI3K, protein kinase B (AKT), p-AKT, mammalian target of rapamycin (mTOR) and p-mTOR were measured by Western blot.Results: miR-6071 was lowly expressed and ULBP2 was highly expressed in GBM tissues and cells. miR-6071 significantly repressed the proliferation, migration and invasion, and promoted apoptosis in GBM cells. Moreover, miR-6071 also inhibited the activation of PI3K/AKT/mTOR pathway in GBM cells. Additionally, miR-6071 has been shown to negatively regulate ULBP2 expression. We also confirmed that ULBP2 could reverse the effects of miR-6071 on GBM cells through regulating PI3K/AKT/mTOR pathway.Conclusion: Our study demonstrated that miR-6071 could suppress cell proliferation, migration and invasion, as well as promote apoptosis through the inhibition of PI3K/Akt/mTOR pathway by binding to ULBP2 in GBM.Keywords: glioblastoma, miR-6071, ULBP2, proliferation, metastasis, PI3K/Akt/mTOR pathway

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