MiRNA-451 plays a role as tumor suppressor in human glioma cells

• Published in: Brain research 2010-11, Vol.1359, p.14-21
• Main Authors: Nan, Yang, Han, Lei, Zhang, Anling, Wang, Guangxiu, Jia, Zhifan, Yang, Yang, Yue, Xiao, Pu, Peiyu, Zhong, Yue, Kang, Chunsheng
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Akt1; Apoptosis - genetics; Biological and medical sciences; Blotting, Western; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Cell Line, Tumor; Cell Proliferation; Elafin - genetics; Elafin - metabolism; Gene Expression; Gene Expression Regulation, Neoplastic - genetics; Genes, Tumor Suppressor; Glioma; Glioma - genetics; Glioma - metabolism; Glioma - pathology; Humans; Malignant phenotype; Medical sciences; MicroRNA-451; MicroRNAs - biosynthesis; MicroRNAs - genetics; Neoplasm Invasiveness - genetics; Neurology; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - genetics; Transfection; Tumors of the nervous system. Phacomatoses; Up-Regulation
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2010.08.074

Abstract MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional and/or translational level by binding loosely complimentary sequences in the 3′untranslated regions (UTRs) of target mRNAs. Increased expressions of several miRNAs, specifically hsa-miR-21, have been reported to modulate glioma development. Here we report downregulation of miR-451 in A172, LN229 and U251 human glioblastoma cells. Increased expression of miR-451 by administration of miR-451 mimics oligonucleotides reversed the biology of each of the three cell lines, inhibiting cell growth, inducing G0/G1 phase arrest and increasing cell apoptosis. Further, treatment with miR-451 mimics oligonucleotides diminished the invasive capacity of these cells, as the number of cells invading through matrigel was significantly decreased. Akt1, CyclinD1, MMP-2, MMP-9 and Bcl-2 protein expression decreased, and p27 expression increased in a dose-dependent manner with miR-451 mimics oligonucleotides. Taken together, these studies reveal miR-451 impacts glioblastoma cell proliferation, invasion and apoptosis, perhaps via regulation of the PI3K/AKT signaling pathway. We propose an essential role for miR-451 as a tumor-suppressor of human glioma.