RESUMO
Circular RNA is a newly discovered member of non-coding RNA (ncRNA) and regulates the target gene by acting as a micro-RNA sponge. It plays vital roles in various diseases. However, the functions of circular RNA in non-small cell lung cancer (NSCLC) remain still unclear. Our data showed that circ-WHSC1 was highly expressed in NSCLC cells and tissues. Both in vitro and in vivo experiments showed that circ-WHSC1 promoted NSCLC proliferation. circ-WHSC1 also promoted the migration and invasion of lung cancer cells. Through bioinformatic analysis and functional experiments, we showed that circ-WHSC1 could act as a sponge for micro-RNA-7 (miR-7) and regulate the expression of TAB2 (TGF-beta activated kinase one binding protein two). Inhibition of the circ-WHSC1/miR-7/TAB2 pathway could effectively attenuate lung cancer progression. In summary, this study confirmed the existence and oncogenic function of circ-WHSC1 in NSCLC. The research suggests that the circ-WHSC1/miR-7/TAB2 axis might be a potential target for NSCLC therapy.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Regulação Neoplásica da Expressão Gênica , Histona-Lisina N-Metiltransferase/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Oncogenes , RNA Circular/genética , Proteínas Repressoras/genética , Animais , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas , Linhagem Celular Tumoral , Proliferação de Células/genética , Modelos Animais de Doenças , Xenoenxertos , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Camundongos , Interferência de RNA , Proteínas Repressoras/metabolismoRESUMO
Purpose: Patients with lung cancer with bone metastasis (LCBM) often have a very poor prognosis. The purpose of this study is to characterize the prevalence and associated factors and to develop a prognostic nomogram to predict the overall survival (OS) and cancer-specific survival (CSS) for patients with LCBM using multicenter population-based data. Methods: Patients with LCBM at the time of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER) Program database of the National Cancer Institute (NCI) from 2010 to 2015. Multivariable and univariate logistic regression analyses were performed to identify factors associated with all-cause mortality and lung cancer (LC)-specific mortality. The performance of the nomograms was evaluated with the calibration curves, area under the curve (AUC), and decision curve analysis (DCA). Kaplan-Meier analysis and log-rank tests were used to estimate the survival times of patients with LCBM. Results: We finally identified 26,367 patients with LCBM who were selected for survival analysis. Multivariate analysis demonstrated age, sex, T stage, N stage, grade, histology, radiation therapy, chemotherapy, primary site, primary surgery, liver metastasis, and brain metastasis as independent predictors for LCBM. The AUC values of the nomogram for the OS prediction were 0.755, 0.746, and 0.775 in the training cohort; 0.757, 0.763, and 0.765 in the internal validation cohort; and 0.769, 0.781, and 0.867 in the external validation cohort. For CSS, the values were 0.753, 0.753, and 0.757 in the training cohort; 0.753, 0.753, and 0.757 in the internal validation cohort; and 0.767, 0.774, and 0.872 in the external validation cohort. Conclusions: Our study constructs a new prognostic model and clearly presents the clinicopathological features and survival analysis of patients with LCBM. The result indicated that the nomograms had favorable discrimination, good consistency, and clinical benefits in patients. In addition, our constructed nomogram prediction models may assist physicians in evaluating individualized prognosis and deciding on treatment for patients.