RNA editing is a widespread post-transcriptional mechanism that confers specific and reproducible nucleotide changes in selected RNA transcripts and plays a critical role in many human cancers. However, little is known about how RNA editing operates in non-small-cell lung cancers. Here, we measured the sequence and expression level of genes of antizyme inhibitor 1 and adenosine deaminase acting on RNA family in 30 non-small-cell lung cancer patient samples and 13 cell lines and revealed RNA editing S367G in antizyme inhibitor 1 is a high-frequent molecular events. We determined overexpression of antizyme inhibitor 1 with RNA editing, implying the oncogenic function of this alteration. We also detected the association of adenosine deaminase acting on RNA overexpression with RNA editing occurred in antizyme inhibitor 1. Furthermore, the RNA editing could cause a cytoplasmic-to-nuclear translocation of antizyme inhibitor 1 protein and conferred the malignant phenotype of non-small-cell lung cancer cells. The in vivo experiment confirmed that this RNA editing confers higher capacity of tumor migration as well. In conclusion, antizyme inhibitor 1 RNA editing and its involvement in tumorigenesis of non-small-cell lung cancer pave a new way for potential clinical management of non-small-cell lung cancer.

An increased risk of non-small cell lung cancer (NSCLC) in cystic fibrosis (CF) patients and carriers of CF transmembrane conductance regulator (CFTR) mutations has been proposed. However, the role of CFTR in lung cancer remains controversial. In the present study, CFTR expression was assessed in 165 NSCLC tumors and 22 normal lung samples with validation in an independent series of 131 samples. The effect of gain and loss of CFTR on the malignant behavior of NSCLC was examined. The effect of CFTR manipulation on tumor metastasis was examined in a mouse model. Expression of CFTR was downregulated in NSCLC (p=0.041). Low CFTR expression was correlated with advanced stage (p<0.001) and lymph node metastasis (p=0.009). Low CFTR expression was significantly associated with poor prognosis (overall survival: 45 vs. 36 months, p<0.0001; progression-free survival: 41 vs. 30 months, p=0.007). Knockdown of CFTR in NSCLC cells enhanced malignant behavior (epithelial-mesenchymal transition, invasion and migration); in contrast, overexpression of CFTR suppressed cancer progression in vitro and in vivo. The tumor-suppressing effect of CFTR was associated with inhibition of multiple uPA/uPAR-mediated malignant traits in culture. These results show that CFTR plays a role in inhibition of NSCLC metastasis and suggest that CFTR may serve as a novel indicator for predicting adverse prognosis and metastasis in NSCLC patients.

BackgroundThe mouse is an organism that is widely used as a mammalian model for studying human physiology or disease, and the development of immunodeficient mice has provided a valuable tool for basic and applied human disease research. Following the development of large-scale mouse knockout programs and genome-editing tools, it has become increasingly efficient to generate genetically modified mouse strains with immunodeficiency. However, due to the lack of a standardized system for evaluating the immuno-capacity that prevents tumor progression in mice, an objective choice of the appropriate immunodeficient mouse strains to be used for tumor engrafting experiments is difficult.MethodsIn this study, we developed a tumor engraftment index (TEI) to quantify the immunodeficiency response to hematologic malignant cells and solid tumor cells of six immunodeficient mouse strains and C57BL/6 wild-type mouse (WT).ResultsMice with a more severely impaired immune system attained a higher TEI score. We then validated that the NOD-scid-IL2Rg−/− (NSI) mice, which had the highest TEI score, were more suitable for xenograft and allograft experiments using multiple functional assays.ConclusionsThe TEI score was effectively able to reflect the immunodeficiency of a mouse strain.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-015-0156-y) contains supplementary material, which is available to authorized users.