Investigate the role of regulator of chromosome condensation 2 () on lung adenocarcinoma (LUAD) metastasis. Clinical specimens were used to assess the impact of RCC2 on LUAD metastasis. Mouse models, cytobiology, and molecular biology assays were performed to elucidate the function and underlying mechanisms of RCC2 in LUAD. RCC2 expression was frequently increased in LUADs (88/122, 72.13%). It was confirmed by analysis of a larger cohort of TCGA RNA-seq data containing 488 LUADs and 58 normal lung tissues ( < 0.001). Importantly, increased level of RCC2 was significantly associated with T status of tumor ( = 0.002), lymph node metastasis ( = 0.004), and advanced clinical stage ( = 0.001). Patients with LUAD with higher expression of RCC2 had shorter overall survival. Cox regression analysis demonstrated that RCC2 was an independent poorer prognostic factor for patients with LUAD. Moreover, forced expression of RCC2 promoted intrapulmonary metastasis and significantly enhanced LUAD cell migration, invasion, and proliferation Further study found that RCC2 induced epithelial-mesenchymal transition (EMT) and also stimulated the expression of MMP-2 and MMP-9. In addition, RCC2 was able to activate JNK, while inhibition of JNK suppressed the effect of RCC2 on LUAD cell migration, invasion, EMT, and the expression of MMP-2 and MMP-9. RCC2 plays a pivotal role in LUAD metastasis by inducing EMT via activation of MAPK-JNK signaling. .
Cigarette smoking has been a well-established risk factor of lung cancer for decades. How smoking contributes to tumorigenesis in the lung remains not fully understood. Here we report the results of a genome-wide study of DNA copy number and smoking packyears in a large collection of nonsmall-cell lung cancer (NSCLC) tumors. Genome-wide analyses of DNA copy number and packyears of cigarette smoking were performed on 264 NSCLC tumors, which were divided into discovery and validation sets. The copy number-smoking associations were investigated in three scales: whole-genome, chromosome/arm, and focal regions. We found that heavy cigarette smokers (>60 pack-years) have significantly more copy number gains than non-or light smokers (£60 pack-years) (P = 2.46 × 10 ) but not in heavy smokers (P = 0.52). Focal copy number analyses showed that there are strong associations of copy number and cigarette smoking pack-years in 12q23 (P = 9.69 × 10 −10
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