PPARα Regulates the Proliferation of Human Glioma Cells through miR-214 and E2F2.

Peroxisome proliferator-activated receptor α (PPARα) is a member of the nuclear hormone receptor superfamily and functions as a transcription factor. Previous work showed that PPARα plays multiple roles in lipid metabolism in tissues such as cardiac and skeletal muscle, liver, and adipose tissue. Recent studies have discovered additional roles for PPARα in cell proliferation and metabolism, as well as tumor progression. PPARα is aberrantly expressed in various cancers, and activated PPARα inhibits the proliferation of some tumor cells. However, there have been no studies of PPARα in human gliomas. Here, we show that PPARα is expressed at lower levels in anaplastic gliomas and glioblastoma multiforme (GBM) tissue compared with low-grade gliomas tissue, and low expression is associated with poor patient prognosis. PPARα activates transcription of dynamin-3 opposite strand (DNMO3os), which encodes a cluster of miR-214, miR-199a-3p, and miR-199a-5p microRNAs. Of these, miR-214 is transcribed at particularly high levels. PPARα-induced miR-214 expression causes downregulation of its target E2F2. Finally, miR-214 overexpression inhibits glioma cell growth in vitro and in vivo by inducing cell cycle arrest in G0/G1. Collectively, these data uncover a novel role for a PPARα-miR-214-E2F2 pathway in controlling glioma cell proliferation.

miR­218 inhibits the proliferation of human glioma cells through downregulation of Yin Yang 1.

Malignant glioma is the most common cancer type of the nervous system and the mechanisms driving the occurrence and development remain unclear, preventing effective treatment of this disease. Therefore, novel and efficient therapies for glioma are required. MicroRNAs (miRNAs) are small non­coding RNAs that act as oncogenes or tumor suppressors in human cancer. In the present study, it was confirmed that Yin Yang­1 (YY1), a transcription factor that is part of the polycomb group protein (PcG) family, is a direct target of miR­218 in human glioma cells. It was demonstrated that YY1 promoted glioma cell proliferation and miR­218 could inhibit glioma cell proliferation by targeting YY1, and indirectly reduced the degradation of p53. Together the results indicate that miR­218 functions as a tumor suppressor in human glioma and suggest that overexpression of miR­218 may be a potential strategy for the treatment of human glioma in the future.

[Over-expression of miR-497 promotes the proliferation of U87 glioma cells by targeting neuregulin receptor degradation protein 1].

Objective To investigate the effect of miR-497 over-expression on the proliferation of U87 human glioma cells. Methods We packaged both pGLV3/H1-NC lentivirus as a negative control group and pGLV3/H1-miR-497 lentivirus as an experimental group, and then constructed U87-NC and U87-miR-497 cell lines, respectively. The relationship between miR-497 and neuregulin receptor degradation protein 1 (Nrdp1) was analyzed by luciferase reporter assay in U87 cells; cell colony formation assay was used to detect cell proliferation and flow cytometry to detect cell cycle; the expressions of Nrdp1, AKT and phosphorylated AKT (p-AKT) were determined by Western blotting. Results We successfully packaged pGLV3/H1-NC and pGLV3/H1-miR-497 lentivirus, and obtained stable U87-NC and U87-miR-497 cell lines. When miR-497 was over-expressed in U87 cells, the cell colony formation ability was enhanced compared with the control group U87-NC. The luciferase reporter assay confirmed that miR-497 targeted Nrdp1 in U87 cells. In the stable infected cells, the level of Nrdp1 protein decreased and p-AKT protein increased, while the AKT protein did not change significantly after over-expression of miR-497. Conclusion Over-expression of miR-497 promotes the proliferation of glioma cells U87 by targeting Nrdp1.

Electron transfer through clay monolayer films fabricated by the Langmuir-Blodgett technique.

Hybrid films composed of amphiphilic molecules and clay particles were constructed by the modified Langmuir-Blodgett (LB) method. Clays used were sodium montmorillonite (denoted as mont) and synthetic smectite containing Co(II) ions in the octahedral sites (denoted as Co). Two kinds of amphiphilic molecules were used-[Ru(dC(18)bpy)(phen)2](ClO4)2 (dC(18)bpy = 4,4'-dioctadecyl-2,2'-bipyridyl and phen = 1,10-phenanthroline) (denoted as Ru) and octadecylammonium choloride (ODAH+Cl- or denoted as ODAH). Three kinds of hybrid films (denoted as Ru-mont, Ru-Co, and ODAH-Co films) were prepared by spreading an amphiphilic molecule onto an aqueous suspension of a clay. Atomic force microscopy (AFM) analyses of the films deposited on silicon wafers indicated that closely packed films were obtained at 20 ppm for all the above three cases. Cyclic voltammetry (CV) was measured on an ITO electrode modified with a hybrid film or a monolayer film of pure Ru(II) complex salt (denoted as Ru film). The Ru(II) complexes incorporated in the Ru-mont film lost their redox activity, indicating that montmorillonite layers acted as a barrier against electron transfer. In contrast, the same complexes in the Ru-Co film were electrochemically active with the simultaneous appearance of the redox peaks due to the Co(II)/Co(III) (or Co(II)/Co(IV)) couple. The results implied that electron transfer through cobalt clay layers was possible via mediation by Co(II) ions in a clay sheet. For an aqueous solution containing nitrite ions (NO2-) at pH 3.0, a large catalytic oxidation current was observed for both the electrodes modified with the Ru-mont and Ru-Co films. The results were interpreted in terms of the mechanisms that the charge separation of an incorporated Ru(II) complex took place to produce a pair of a Ru(III) complex and an electron and that the generated Ru(III) complex was reduced by a nitrite ion before it recombined with the electron.