Malignant gliomas are the most common central nervous system tumors and the molecular mechanism driving their development and recurrence is still largely unknown, limiting the treatment of this disease. Here, we show that restoring the expression of miR-218, a microRNA commonly downregulated in glioma, dramatically reduces the migration, invasion, and proliferation of glioma cells. Quantitative reverse transcription PCR and Western blotting analysis revealed that expression of the stem cell-promoting oncogene Bmi1 was decreased after overexpression of miR-218 in glioma cells. Mechanistic investigations defined Bmi1 as a functional downstream target of miR-218 through which miR-218 ablated cell migration and proliferation. We documented that miR-218 also blocked the self-renewal of glioma stem-like cells, consistent with the suggested role of Bmi1 in stem cell growth. Finally, we showed that miR-218 regulated a broad range of genes involved in glioma cell development, including Wnt pathways that suppress glioma cell stem-like qualities. Taken together, our findings reveal miR-218 as a tumor suppressor that prevents migration, invasion, proliferation, and stemlike qualities in glioma cells. Cancer Res; 73(19); 6046-55. Ó2013 AACR.

Gold nanoclusters (GNCs) attract increasing attention due to their potential applications in sensing, catalysis, optoelectronics, and biomedicine. Herein, the formation of highly fluorescent glutathione (GSH)‐capped GNCs is achieved through the delicate control of the reduction kinetics and thermodynamic selection of the Au(I)–SG complexes. Furthermore, the GNCs‐based nanoprobes are developed by the covalent coupling folic acid (FA) and PEG (polyethylene glycol) on the surface of GNCs directly, followed by trapping photosensitizer (chlorin e6, Ce6) within PEG networks and attaching to the GNCs surface. The fabricated nanoprobes (Ce6@GNCs‐PEG2K‐FA) possess a uniform particle size (hydrodynamic diameter ≈6.1 ± 1.2 nm), without affecting the yield of singlet oxygen of the trapped Ce6. In vitro studies show the enhanced cellular uptake and satisfactory photodynamic therapy (PDT) effectiveness toward MGC‐803 cells when compared with free Ce6. The biodistribution and excretion pathway studies of the nanoprobes in MGC‐803 tumor‐bearing nude mice reveal their superior penetration and retention behavior in tumors, while the preserved features of renal clearance and stealthy to reticulo‐endothelial system are mainly attributed to the small hydrodynamic diameters and the FA‐capped PEGylated ligands. The enhanced PDT efficacy and the nontoxicity to mice provide an exciting new nano‐platform with promising clinical translational potential.

Gastric cancer (GC) is the second most common cancer in China and the second leading cause of cancer-related death in the world. Identifying circulating biomarkers is helpful to improve theranostics of gastric cancer. Herein, we are for the first time to report miR-16-5p and miR-19b-3p were identified to be the novel potential plasma biomarkers to detect gastric cancer. Differentially expressed miRNAs were initially screened out by genome-wide miRNA profiling microarrays between 16 plasma samples of gastric cancer and 18 matched normal controls, and then were quantified and validated by quantitative reverse transcription-PCR method between 155 gastric cancer cases and 111 normal controls. Additionally, 30 plasma samples from precancerous lesions and 18 paired samples from gastric cancer patients with gastrectomy were further detected. Results showed that based on two normalization methods, miR-16-5p and miR-19b-3p in plasma were found to be capable of distinguishing normal population from GC cases with different TNM stages and differentiation grades, particularly including the early cancer cases (P<0.05). And the two miRNAs were down-regulated in GC cases (FC<0.5). Especially, the down-regulation degree was correlated with the progression of the GC cases from the early stage to the advanced stage (0.2< rs<0.3, P<0.01). And the same weak down-regulation of the two biomarkers as the early GC occurred initially in the precancerous diseases (P<0.05). The corresponding performance of the two miRNAs to detect GC in ROC analysis gradually performed better with the disease progression from the earlier stages or lower grades to the advanced stages (TNM Ⅳ stage: AUC=0.832 for miR-16-5p; TNM Ⅲ stage: AUC=0.822 for miR-19b-3p) or high grade (Poorly differentiated: AUC=0.801, 0.791 respectively for miR-16-5p and miR-19b-3p). Additionally, miR-19b-3p remained down-regulated in patient plasma within 9 days after gastrectomy. In conclusion, miR-19b-3p and miR-16-5p maybe prospective biomarkers to detect gastric cancer and indicate its progression, and thus may own great potential in applications such as early screening and progression evaluation of gastric cancer in the near future.