Project description:Rationale: Even after quitting smoking, the risk of the development of chronic obstructive pulmonary disease (COPD) and lung cancer remains significantly higher compared to never-smokers. Objectives: Based on the knowledge that COPD and most lung cancers start in the small airway epithelium (SAE), we hypothesized that smoking modulates miRNA expression in the SAE linked to the pathogenesis of smoking-induced airway disease, and that some of these changes persist after smoking cessation. Methods: SAE was collected from 10th to 12th order bronchi using fiberoptic bronchoscopy. Affymetrix miRNA 2.0 arrays were used to assess miRNA expression in the SAE from 10 healthy never-smokers and 10 healthy smokers, before and after they quit for 3 months. Smoking status was determined by urine nicotine and cotinine measurement. Results: There were significant differences in the expression of 34 miRNAs between healthy smokers and healthy never-smokers (p<0.01, fold-change >1.5), with functions associated with lung development, airway epithelium differentiation, inflammation and cancer. After quitting smoking for 3 months, 12 out of the 34 miRNAs did not return to normal levels, with Wnt/β-catenin signaling pathway the top enriched pathway of the target genes of the persistent deregulated miRNAs. Conclusions: In the context that many of these persistent smoking-dependent miRNAs are associated with differentiation, inflammation diseases or lung cancer, it is likely that persistent smoking-related changes in small airway epithelium miRNAs play a role in the subsequent development of these disorders.
Project description:Long noncoding RNAs (lncRNAs) are emerging as key regulators in cancer and play complicate and critical roles in regulating various key biological processes including chromatin modification, transcription and post-transcriptional processing. We identified a novel transcript, lncRNA NMR, which was upregulated in esophageal squamous cell carcinoma (ESCC) and significantly associated with overall survival of ESCC patients and and is identical to ENST00000432429.1 in GENCODE v13 or ENST00000432429.5 in Ensembl release 83. Here, we sought to determine the alterations of trancriptome after shRNA-mediated knockdown and transient overexpression of lncRNA NMR in ESCC KYSE70 and KYSE450 cell lines．
Project description:Cigarette smoke is associated with the majority of lung cancers: however, 25% of lung cancer patients are non-smokers, and half of all newly diagnosed lung cancer patients are former smokers. Lung tumors exhibit distinct epidemiological, clinical, pathological, and molecular features depending on smoking status, suggesting divergent mechanisms underlie tumorigenesis in smokers and non-smokers. MicroRNAs (miRNAs) are integral contributors to tumorigenesis and mediate biological responses to smoking. Based on the hypothesis that smoking-specific miRNA differences in lung adenocarcinomas reflect distinct tumorigenic processes selected by different smoking and non-smoking environments, we investigated the contribution of miRNA disruption to lung tumor biology and patient outcome in the context of smoking status. Results: We discovered novel and distinct smoking-status-specific patterns of miRNA and miRNA-mediated gene networks, and identified miRNAs that were prognostically significant in a smoking-dependent manner. Conclusions: We conclude that miRNAs disrupted in a smoking-status-dependent manner affect distinct cellular pathways and differentially influence lung cancer patient prognosis in current, former and never smokers. Our findings may represent promising biologically relevant markers for lung cancer prognosis or therapeutic intervention.
