No abstract

The detection of nonsmall cell lung cancer (NSCLC) at an early stage presents a daunting challenge due to the lack of a specific noninvasive marker. The discovery of microRNAs (miRNAs), particularly those found in serum, has opened a new avenue for tumor diagnosis. To determine whether the expression profile of serum miRNAs can serve as a NSCLC fingerprint, we performed Taqman probe-based quantitative RT-PCR assay to selected differentially expressed serum miRNAs from a sample set including 400 NSCLC cases and 220 controls, and risk score analysis to evaluate the diagnostic value of the serum miRNA profiling system. After a two-phase selection and validation process, 10 miRNAs were found to have significantly different expression levels in NSCLC serum samples compared with the control serum samples. Risk score analysis showed that this panel of miRNAs was able to distinguish NSCLC cases from controls with high sensitivity and specificity. Under ROC curves, the AUC for tumor identification in training set and validation set were 0.966 and 0.972, respectively. Furthermore, the expression profile of the 10-serum miRNAs was correlated with the stage of NSCLC patients, especially in younger patients and patients with current smoking habits. More importantly, the serum miRNA-based biomarker for early NSCLC detection was supported by a retrospective analysis in which the 10-serum miRNA profile could accurately classify serum samples collected up to 33 months ahead of the clinical NSCLC diagnosis. Taken together, we demonstrate that the profiling of 10-serum miRNAs provides a novel noninvasive biomarker for NSCLC diagnosis.Lung cancer is the most common cancer in the world and the leading cause of cancer-related deaths in developed countries. Nonsmall cell lung cancer (NSCLC) accounts for 75 to 80% of lung cancer cases.1-3 So far, the most effective treatment for NSCLC is surgical resection, which is limited by the fact that 65% of patients have advanced disease at the time Key words: serum microRNA, nonsmall cell lung cancer, early diagnosis, noninvasive biomarker Additional Supporting Information may be found in the online version of this article

PGC-1a mRNA and protein are elevated in islets from multiple animal models of diabetes. Overexpression of PGC-1a impairs glucose-stimulated insulin secretion (GSIS). However, it is not well known which metabolic events lead to upregulation of PGC-1a in the b-cells under pathophysiological condition. In present study, we have investigated effects of chronic hyperlipidemia and hyperglycemia on PGC-1a mRNA expression in isolated rat islets. Isolated rat islets are chronically incubated with 0, 0.2 and 0.4 mM oleic acid/palmitic acid (free fatty acids, FFA) or 5.5 and 25 mM glucose for 72 h. FFA dose-dependently increases PGC-1a mRNA expression level in isolated islets. FFA also increases PGC-1a expression in mouse b-cell-derived bTC3 cell line. In contrast, 25 mM glucose decreases expression level of PGC-1a. Inhibition of PGC-1a by siRNA improves FFA-induced impairment of GSIS in islets. These data suggest that hyperlipidemia and hyperglycemia regulate PGC-1a expression in islets differently, and elevated PGC-1a by FFA plays an important role in chronic hyperlipidemia-induced b-cell dysfunction.

How polyphagous herbivores up-regulate their counterdefense genes in response to a broad range of structurally different allelochemicals remains largely unknown. To test whether this is accomplished by having more allelochemical-response elements or the similar number of functionally more diverse elements, we mapped out the cis-acting elements mediating the induction of the allelochemical-metabolizing CYP321A1 from the generalist Helicoverpa zea by xanthotoxin and flavone, two structurally distinct allelochemicals with very different encounter rate by this species. Seven xanthotoxin-responsive elements were localized by analyzing promoter activities of varying length of CYP321A1 promoter in H. zea fatbody cells. Compared with the 5 flavone-responsive elements mapped out previously, there are four common elements (1 essential element, 2 enhancers, and 1 negative element) mediating induction of CYP321A1 by both of the two allelochemicals. The remaining four elements (3 enhancers and 1 negative element), however, only regulate induction of CYP321A1 by either of the two allelochemicals. Co-administration of the two allelochemicals resulted in an induction fold that is significantly lower than the expected additive value of the two allelochemicals. These results indicate that xanthotoxin- and flavone-induced expressions of CYP321A1 are mediated mainly by the functionally more diverse common elements although the allelochemical-unique elements also play a role.