No abstract

Copper-transporting P-type adenosine triphosphatase A (ATP7A) is associated with platinum drug resistance in non-small cell lung cancer (NSCLC). microRNAs (miRNAs) are a class of small non-coding RNA molecules that regulate gene expression at post-transcriptional level. In this study, the aim is to explore which miRNAs might participate in the platinum resistance by targeting ATP7A in NSCLC. Using real-time PCR-based miRNA expression profiling and bioinformatics, we selected miR-495 as a candidate miRNA. EGFP reporter assay, real-time PCR, and Western blot validated that ATP7A was a direct target for miR-495. The drug sensitivity assay indicated that miR-495 enhanced the cell response to cisplatin (CDDP) in NSCLC cells, while inhibition of miR-495 led to the opposite effects. Importantly, either overexpression or knockdown of ATP7A could override the effect of miR-495 on chemosensitivity. We also demonstrated that miR-495 increased the intracellular CDDP accumulation and overexpression of ATP7A can reduce the increased drug concentration induced by miR-495. Finally, we discovered that there was a converse relationship between miR-495 and ATP7A levels in NSCLC tissues sensitive or resistant to CDDP. In conclusion, our data demonstrate that miR-495 regulates the multi-drug resistance by modulation of ATP7A expression in NSCLC and suggest that miR-495 may serve as a potential biomarker for the treatment of multi-drug resistant NSCLC patients with high ATP7A levels.

Emerging evidence suggests that diffusion-weighted magnetic resonance imaging (DW MRI) could be useful for tumor detection with N and M staging of lung cancer in place of fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). DW MRI at 3.0 T and FDG PET/CT were performed before therapy in 113 patients with pulmonary nodules. Mean apparent diffusion coefficient (ADC), maximal standardized uptake value (SUVmax ) and Ki-67 scores were assessed. Quantitatively, specificity and accuracy of ADC (91.7 and 92.9%, respectively) were significantly higher than those of SUVmax (66.7 and 77.9% respectively, p < 0.05), although sensitivity was not significantly different between them (93.5 and 83.1%, p > 0.05). Qualitatively, sensitivity, specificity and accuracy of DW MRI (96.1, 83.3 and 92.0%, respectively) were also not significantly different from that of FDG PET/CT (88.3, 83.3 and 86.7%, respectively, p > 0.05). Significant negative correlation was found between Ki-67 score and ADC (r = -0.66, p < 0.05), ADC and SUVmax (r = -0.37, p < 0.05), but not between Ki-67 score and SUVmax (r = -0.11, p > 0.05). In conclusion, quantitative and qualitative assessments for detection of malignant pulmonary tumors with DW MRI at 3.0 T are superior to those with FDG PET/CT. Furthermore, ADC could predict the malignancy of lung cancer.