<p>MicroRNA-652 suppresses malignant phenotypes in glioblastoma multiforme via FOXK1-mediated AKT/mTOR signaling pathway</p>

Abstract

Purpose An increasing number of studies have documented that dysregulation of microRNAs (miRNAs) is common in glioblastoma multiforme (GBM). miR-652 is aberrantly expressed in various human cancers and plays important roles in numerous cancer-related processes. However, the expression profiles and potential roles of miR-652 in GBM remain largely unknown. Patients and methods Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine miR-652 expression in GBM tissues and cell lines. The effects of miR-652 upregulation on GBM cell proliferation, clone formation, apoptosis, migration and invasion were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, clone formation, flow cytometry and Transwell ® migration and invasion assays, respectively. In vivo xenotransplantation was utilized to determine the effect of miR-652 on GBM tumor growth in vivo. Of note, the molecular mechanisms underlying the tumor-suppressing activity of miR-652 upregulation in GBM cells were also investigated using a series of experiments, including bioinformatics analysis, luciferase reporter assay, RT-qPCR and Western blot analysis. Results miR-652 expression was considerably downregulated in GBM tissues and cell lines. Low miR-652 expression was strongly correlated with Karnofsky performance score and tumor size. Overall survival duration was shorter in GBM patients with low miR-652 expression than in those with high miR-652 expression. miR-652 resumption considerably suppressed the proliferation, clone formation, migration, and invasion and promoted the apoptosis of GBM cells in vitro. In addition, forkhead-box k1 (FOXK1) was demonstrated as the direct target gene of miR-652 in GBM cells. FOXK1 downregulation led to a tumor-suppressing activity similar to that of miR-652 upregulation. Restoration of FOXK1 expression partially neutralized the influence of miR-652 overexpression on GBM cells. Furthermore, ectopic miR-652 expression deactivated the AKT/mTOR pathway in GBM cells via FOXK1 regulation. Moreover, miR-652 impaired GBM tumor growth in vivo, probably caused by miR-652-mediated suppression of FOXK1/AKT/mTOR signaling. Conclusion miR-652 inhibits FOXK1 and deactivates the AKT/mTOR pathway, thereby resulting in the suppression of malignant phenotypes of GBM cells in vitro and in vivo.

Mir-139-5p inhibits glioma cell proliferation and progression by targeting GABRA1

“…MiRNAs are a group of short and non-coding RNA molecules that influence the biological characteristics of GBM cells [8,9]. Mounting evidence has shown that miRNAs can act as cancer-suppressing factors as well as oncogenes [10][11][12]. MiRNAs play important roles in the tumorigenesis and progression, invasion, and metastasis of GBM by upregulating or downregulating cancer-related gene expression levels, and, therefore, have become promising biomarkers in the diagnosis and prognosis glioma [13].…”

The Role of Micro RNAs in Regulating PI3K/AKT Signaling Pathways in Glioblastoma

“…In addition, miR-489 and miR-326 via targeting SPIN1 and PKM2, respectively, can modulate the PI3K/AKT-/mTOR pathway to increase apoptosis and decrease invasion (63,64). Interestingly, miR-652 plays an influential role in reducing tumor size in a patient with glioblastoma; miR-652 deactivates the AKT/mTOR pathway through its direct target FOXK1 (65).…”