Serum microRNAs have been identified as potential cancer biomarkers. However, the detailed mechanism by which expression of microRNAs contributes to the development and diagnosis of NSCLC remains unknown. This study was to identify specific miRNAs for diagnosing or predicting the prognosis of NSCLC patients and their correlation between miRNA expression in tissues and serums. Six matched cancer and noncancerous tissues from NSCLC patients were analyzed by miRNA microarray. Among these, three miRNAs (miR-21, miR-141, and miR-200c) were examined in 70 NSCLC paired samples (cancer, normal tissue, and serum) and 44 serum samples of normal volunteers by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Consisting with the microarray results, the expression levels of miR-21, miR-141, and miR-200c in NSCLC were higher than those in normal tissues. While the level of serum miR-21 was increased in cancer patients as compared with that in normal counterpart, expression of miR-141 and miR-200c showed lower levels in serums from cancer patients. Overexpression of serum miR-21 was strongly associated with lymph node metastasis and advanced clinical stage of NSCLC. Finally, log-rank and Cox regression tests demonstrated that high expressions of tumor miR 21 and miR-200c or serum miR-21 were associated with a poor survival in NSCLC patients. Our results suggest that tumor miR-21, miR-141, miR-200c, and serum miR-21 may be potential novel biomarkers for the diagnosis of NSCLC. In addition, this study, for the first time, identifies a significant role of the tumor miR-200c played in predicting prognosis in patients with NSCLC.

Glucose metabolism in vertebrate retinas is dominated by aerobic glycolysis (the “Warburg Effect”), which allows only a small fraction of glucose-derived pyruvate to enter mitochondria. Here, we report evidence that the small fraction of pyruvate in photoreceptors that does get oxidized by their mitochondria is required for visual function, photoreceptor structure and viability, normal neuron–glial interaction, and homeostasis of retinal metabolism. The mitochondrial pyruvate carrier (MPC) links glycolysis and mitochondrial metabolism. Retina-specific deletion of MPC1 results in progressive retinal degeneration and decline of visual function in both rod and cone photoreceptors. Using targeted-metabolomics and 13C tracers, we found that MPC1 is required for cytosolic reducing power maintenance, glutamine/glutamate metabolism, and flexibility in fuel utilization.

Metabolite transport is a major function of the retinal pigment epithelium (RPE) to support the neural retina. RPE dysfunction plays a significant role in retinal degenerative diseases. We have used mass spectrometry with C tracers to systematically study nutrient consumption and metabolite transport in cultured human fetal RPE. LC/MS-MS detected 120 metabolites in the medium from either the apical or basal side. Surprisingly, more proline is consumed than any other nutrient, including glucose, taurine, lipids, vitamins, or other amino acids. Besides being oxidized through the Krebs cycle, proline is used to make citrate via reductive carboxylation. Citrate, made either fromC proline or from C glucose, is preferentially exported to the apical side and is taken up by the retina. In conclusion, RPE cells consume multiple nutrients, including glucose and taurine, but prefer proline, and they actively synthesize and export metabolic intermediates to the apical side to nourish the outer retina.

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