Tumor cells metabolize more glucose to lactate in aerobic or hypoxic conditions than non-tumor cells. Pyruvate kinase isoenzyme type M2 (PKM2) is crucial for tumor cell aerobic glycolysis. We established a role for let-7a/c-Myc/hnRNPA1/PKM2 signaling in glioma cell glucose metabolism. PKM2 depletion via siRNA inhibits cell proliferation and aerobic glycolysis in glioma cells. C-Myc promotes up-regulation of hnRNPA1 expression, hnRNPA1 binding to PKM pre-mRNA, and the subsequent formation of PKM2. This pathway is downregulated by the microRNA let-7a, which functionally targets c-Myc, whereas hnRNPA1 blocks the biogenesis of let-7a to counteract its ability to downregulate the c-Myc/hnRNPA1/PKM2 signaling pathway. The down-regulation of c-Myc/hnRNPA1/PKM2 by let-7a is verified using a glioma xenograft model. These results suggest that let-7a, c-Myc and hnRNPA1 from a feedback loop, thereby regulating PKM2 expression to modulate glucose metabolism of glioma cells. These findings elucidate a new pathway mediating aerobic glycolysis in gliomas and provide an attractive potential target for therapeutic intervention.

Aerobic glycolysis (production of lactate from glucose in the presence of oxygen) is a hallmark of cancer. Fenofibrate is a lipid-lowering drug and an agonist of the peroxisome proliferator-activated receptor alpha (PPARα). We found that FF inhibited glycolysis in a PPARα-dependent manner in glioblastoma cells. Fenofibrate inhibited the transcriptional activity of NF-κB/RelA and also disrupted its association with hypoxia inducible factor1 alpha (HIF1α), which is required for the binding of NF-κB/ RelA to the PKM promoter and PKM2 expression. High ratios of PKM2/PKM1 promote glycolysis and inhibit oxidative phosphorylation, thus favoring aerobic glycolysis. Fenofibrate decreased the PKM2/PKM1 ratio and caused mitochondrial damage. Given that fenofibrate is a widely used non-toxic drug, we suggest its use in patients with glioblastoma multiforme (GBM).

Magnetic separation with composite microspheres presents an alternative strategy for applications in biomedical and bioengineering fields. However, the synthesis of core-shell structured magnetic composites universally assumes the surfactant-directing and/or silica-assisting polymerization approach to modify and stabilize the magnetic cores. In this paper, we report on the surfactant-free synthesis of well-defined core-shell structured Fe(3)O(4)@PANI and Fe(3)O(4)@PPy microspheres with high magnetization. The temperature dependence of magnetization of the samples was examined as a function of temperature between 3 and 300 K in an applied field of 500 Oe. It was found that the blocking temperature (T(B)) values of the composite spheres are well above the room temperature. The small variation in magnetization as the temperature changes renders the composite spheres a suitable candidate when used at elevated temperatures. Also, the genomic DNA can be effectively isolated from Aspergillus niger (A. niger) cells with the composite microspheres, using a PEG-NaCl binding buffer and a phosphate eluting buffer. The magnetic isolation of genomic DNA with the composite microspheres was shown to be superior to the conventional phenol-chloroform extraction, which was confirmed by agarose gel eletrophoresis and polymerase chain reaction (PCR) diagnosis. The Fe(3)O(4)@PANI and Fe(3)O(4)@PPy microspheres presented here have great potential in enzyme immobilization, drug delivery, catalysis, and sensors.