MicroRNA miR-451 downregulates the PI3K/AKT pathway through CAB39 in human glioma
Open Access
- 15 December 2011
- journal article
- Published by Spandidos Publications in International Journal of Oncology
- Vol. 40 (4), 1105-1112
- https://doi.org/10.3892/ijo.2011.1306
Abstract
The microRNA miR-451 is downregulated in gliomas, this has been suggested by several different research groups and is consistent with our data. Our previous study also confirmed that miR-451 has a repressive role in glioma by inhibiting cell growth, proliferation and by inducing cell apoptosis. In the present study, we identified a target gene of miR-451 in human glioma and investigated the mechanism for the glioma suppressive effect of miR-451 functions. Expression of miR-451 in gliomas was identified by quantitative real-time PCR and fluorescence in situ hybridization. Human glioma cell lines (U251, U87, LN229 and A172) were transfected with miR-451 mimics to restore miR-451 expression. The tumor suppressive effects of miR-451 were further verified by subcutaneous assays in nude mice, in addition to our previous in vitro data. A candidate target gene was tested by Western blotting and luciferase reporter assays. Some PI3K/AKT pathway factors were tested by Western blotting. We found that miR-451 expression was downregulated in glioma samples and was inversely correlated with WHO grades of gliomas. In vivo assays confirmed that miR-451 had tumor suppressive traits. CAB39-3'UTR luciferase reporter assay confirmed CAB39 as a direct target gene of miR-451. Significant alterations in the expression of PI3K/AKT pathway factors were observed by Western blot assays. We conclude that miR-451 represses glioma in vitro and in vivo, likely through targeting CAB39 directly and inhibiting the PI3K/AKT pathway indirectly.Keywords
This publication has 40 references indexed in Scilit:
- MiR-221 and miR-222 target PUMA to induce cell survival in glioblastomaMolecular Cancer, 2010
- Exciting New Advances in Neuro-Oncology: The Avenue to a Cure for Malignant GliomaCA: A Cancer Journal for Clinicians, 2010
- Argonaute HITS-CLIP decodes microRNA–mRNA interaction mapsNature, 2009
- MicroRNA-21 modulates biological functions of pancreatic cancer cells including their proliferation, invasion, and chemoresistanceMolecular Cancer Therapeutics, 2009
- MicroRNA-27a functions as an oncogene in gastric adenocarcinoma by targeting prohibitinCancer Letters, 2009
- MIR-451 and Imatinib mesylate inhibit tumor growth of Glioblastoma stem cellsBiochemical and Biophysical Research Communications, 2008
- MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiationNature, 2008
- Widespread changes in protein synthesis induced by microRNAsNature, 2008
- Malignant astrocytic glioma: genetics, biology, and paths to treatmentGenes & Development, 2007
- MicroRNAs: small RNAs with a big role in gene regulationNature Reviews Genetics, 2004