MicroRNA-7 directly targets insulin-like growth factor 1 receptor to inhibit cellular growth and glucose metabolism in gliomas

Abstract

BackgroundRecent studies observed that altered energy metabolism has become widespread in cancer cells along with other cancer-associated traits that have been accepted as hallmarks of cancer. Akt signaling pathway is involved in the aerobic glycolysis program. However, mechanisms underlying the regulation of aerobic glycolysis and Akt activity in gliomas remain unclear. MicroRNAs are a group of small non-coding RNAs that can function as endogenous RNA interference to regulate expression of targeted genes. This study was conducted to detect the function of miR-7 targeting insulin-like growth factor 1 receptor (IGF-1R), which is an upstream regulator of Akt.MethodsMicroRNA expression data for gliomas and normal controls were downloaded from The Cancer Genome Atlas (TCGA) database. Quantitative real-time PCR was used to measure the microRNA-7 (miR-7) expression level, and Western blot was performed to detect protein expression in U87 and U251 cells. Colony formation assay and glycolysis stress test were also conducted. Luciferase reporter assay was used to identify the mechanism of IGF-1R and miR-7 regulation.ResultsmiR-7 was downregulated in human glioma tissues based on TCGA database. Forced expression of miR-7 or IGF-1R knockdown inhibited colony formation and glucose metabolic capabilities of glioma cells in vitro and decreased the p-Akt expression level. Bioinformatics analysis results indicated that IGF-1R could be a target of miR-7. Western blot and luciferase reporter assays showed that miR-7 modulated IGF-1R expression by directly targeting the binding site within the 3′-untranslated region.ConclusionsThis study provides the first evidence that miR-7 inhibits cellular growth and glucose metabolism in gliomas, at least partially, by regulating the IGF-1R/Akt signaling pathway. Therefore, miR-7 is a promising molecular drug for glioma treatment.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_211

Caffeine-induced nuclear translocation of FoxO1 triggers Bim-mediated apoptosis in human glioblastoma cells

“…Western blot analysis was performed as described previously [20]. Immunoblot was performed using the appropriate primary antibodies: FoxO1 (1:1000; CST, USA), Bim (1:1000; CST, USA), and GAPDH (1:1000; CST, USA).…”

“…A colony formation assay was performed as described previously [20]. Glioma cells were seeded at 5×10 2 cells/plate onto 60-mm tissue culture plates and different concentrations of caffeine (0, 1, and 5 mM) were added.…”

Role of microRNA-7 in digestive system malignancy

“…Also, miR-7 is expressed abundantly in human pancreas and endocrine cells and has a specific role in endocrine cell differentiation and function [10] . It has been demonstrated that miR-7 is a tumor suppressor in breast, lung and ovarian cancers, and glioblastoma, mainly focusing on its relationship with EGFR [11][12][13][14][15] . Accumulating evidence shows that miR-7 can simultaneously target a variety of mRNAs involved in diverse signaling pathways in different tumors.…”

AKT-induced PKM2 phosphorylation signals for IGF-1-stimulated cancer cell growth

“…IGFs, a growth factor family promoting cancer development and progression [4–6], are involved in the alteration of energy metabolism in cancer cells, specifically aerobic glycolysis [18, 32, 33]. PKM2 protein undergoes post-translational modifications in response to growth factor signals, whereby it acquires cancer-promoting functions [25, 26, 28, 31]].…”